0%
RAD51Bc.476G>ALikely benign
Print report
Variant interpretation report

RAD51B c.476G>A, p.(Arg159His)

NM_133509.4:c.476G>A NP_598193.2:p.(Arg159His) View identifiers
Classification
Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About RAD51B

No gene-level summary was recorded for this case.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 3
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3
BS1Supporting
BS1 · supporting

This variant exceeds the 0.3% allele frequency threshold for a presumed dominant disorder in the South Asian subpopulation. In gnomAD v2.1, the SAS AF is 0.358% (109/30,430 alleles) with 1 homozygote, and in gnomAD v4.1, the SAS AF is 0.337% (305/90,530 alleles) with 3 homozygotes. The grpmax filtering allele frequency is 0.303% (v2.1). The presence of homozygous individuals in a population database further supports that this variant is too common to be a highly penetrant pathogenic variant. Assessed at supporting strength rather than strong benign due to the population-specific nature of the elevated frequency.

BP4Supporting
BP4 · supporting

Multiple lines of computational evidence consistently predict no damaging effect: REVEL score 0.385 (below the published 0.5 threshold for pathogenicity), BayesDel score 0.129 (near-zero, consistent with benign impact), and SpliceAI max delta score 0.00 (no predicted splice alteration). All available in silico tools agree on a benign prediction.

BP6Supporting
BP6 · supporting

This variant is classified as Likely benign in ClinVar (Variation ID 1678949) by three clinical laboratories: Ambry Genetics, PreventionGenetics (part of Exact Sciences), and the National Health Laboratory Service. While the review status is 'criteria provided, single submitter' and no expert panel review has been performed, the consensus from multiple clinical testing laboratories supports a benign interpretation.

Recorded classification: Likely benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 supporting, BP4 supporting, BP6 supporting; combination = 3 supporting benign, which maps to Likely Benign.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1
gnomAD v2.1
Population frequency
384 / 1,608,480 alleles

gnomAD v4.1: 384 / 1,608,480 alleles. Recorded AF 0.000238735. Recorded homozygote count 3.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.000418624; MAF= 0.04186%, 118/281876 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00358199; MAF= 0.35820%, 109/30430 alleles, homozygotes = 1); grpmax FAF= 0.00303643.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0006515365403409708, 12/18418 alleles, homozygotes = 0).

Applied · BS1 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
Functional evidence
Statement recorded

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. RAD51B, a DNA repair protein involved in homologous recombination, is altered by mutation in various cancer types.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
2 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV66846898, n = 2 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

26 criteria with recorded statuses: 3 met · 8 not met · 12 not assessed · 3 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_133509.4:c.476G>A (p.Arg159His) in RAD51B is classified as Likely benign based on three supporting benign criteria per the generic ACMG/AMP 2015 framework (PMID:25741868). The generic ACMG combination rules require ≥2 supporting benign criteria for Likely benign classification.

The variant exceeds the 0.3% BS1 allele frequency threshold in the South Asian subpopulation (gnomAD v2.1 SAS AF = 0.358%, 109/30,430 alleles, 1 homozygote; gnomAD v4.1 SAS AF = 0.337%, 305/90,530 alleles, 3 homozygotes; grpmax FAF = 0.303%), indicating it is too common to be a highly penetrant pathogenic variant (BS1_supporting).

Multiple in silico tools predict a benign impact: REVEL score 0.385 (below 0.5 threshold), BayesDel score 0.129 (near-zero), and SpliceAI max delta 0.00 (no splice impact), meeting BP4_supporting.

ClinVar reports this variant as Likely benign from three clinical testing laboratories (Ambry Genetics, PreventionGenetics, NHLS; Variation ID 1678949), meeting BP6_supporting.

No pathogenic or likely pathogenic criteria were met. PVS1 does not apply to this missense variant. PS3/PS4 are not met due to absence of variant-specific functional or case-control data. PM2 is not met as the variant frequency exceeds 0.1% in the South Asian population. PP3 is not met because all in silico tools predict a benign effect. PP5 is not met as ClinVar reports Likely benign, not pathogenic.

Met · 3

BS1 SupportingThis variant exceeds the 0.3% allele frequency threshold for a presumed dominant disorder in the South Asian subpopulation. In gnomAD v2.1, the SAS AF is 0.358% (109/30,430 alleles) with 1 homozygote, and in gnomAD v4.1, the SAS AF is 0.337% (305/90,530 alleles) with 3 homozygotes. The grpmax filtering allele frequency is 0.303% (v2.1). The presence of homozygous individuals in a population database further supports that this variant is too common to be a highly penetrant pathogenic variant. Assessed at supporting strength rather than strong benign due to the population-specific nature of the elevated frequency. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 SAS: AF=0.358% (>0.3%)
  • 109/30
  • 430
  • 1 homozygote
  • gnomAD v4.1 SAS: AF=0.337% (>0.3%)
  • 305/90
  • 530
  • 3 homozygotes
  • grpmax FAF v2.1: 0.303% (>0.3%)
Still missing
  • RAD51B penetrance estimates to refine BS1 allele frequency threshold
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP4 SupportingMultiple lines of computational evidence consistently predict no damaging effect: REVEL score 0.385 (below the published 0.5 threshold for pathogenicity), BayesDel score 0.129 (near-zero, consistent with benign impact), and SpliceAI max delta score 0.00 (no predicted splice alteration). All available in silico tools agree on a benign prediction. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.385 (below 0.5 damaging threshold
  • benign-leaning)
  • BayesDel: 0.129 (near-zero
  • likely benign)
  • SpliceAI: max delta 0.00 (no splice impact predicted)
Sources
revelbayesdelspliceai ↗
BP6 SupportingThis variant is classified as Likely benign in ClinVar (Variation ID 1678949) by three clinical laboratories: Ambry Genetics, PreventionGenetics (part of Exact Sciences), and the National Health Laboratory Service. While the review status is 'criteria provided, single submitter' and no expert panel review has been performed, the consensus from multiple clinical testing laboratories supports a benign interpretation. Details ▾Hide ▴
Evidence considered
  • ClinVar Variation ID 1678949: Likely benign from 3 clinical laboratories
  • Submitters: Ambry Genetics
  • PreventionGenetics/Exact Sciences
  • NHLS Universitas
Still missing
  • Expert panel or CSPEC review would strengthen benign classification consensus
Sources
clinvar ↗

Not met · 8 · evaluated, threshold not reached

PVS1 NM_133509.4:c.476G>A is a missense variant (p.Arg159His), not a null variant (nonsense, frameshift, or canonical ±1,2 splice site). The generic PVS1 framework (PMC6185798) does not apply to missense substitutions in the 'other' variant bucket. Although RAD51B loss of function is a supported germline disease mechanism, this specific alteration does not meet PVS1 eligibility. Details ▾Hide ▴
Evidence considered
  • PVS1 variant assessment: bucket=other
  • apply_generic_pvs1_framework=false
  • RAD51B LoF mechanism supported by germline literature (PMID:25600502
  • PMID:26351136
  • PMID:38041901)
  • Variant is a missense substitution
  • not a predicted null variant
Sources
pvs1_generic_framework ↗pvs1_gene_contextpvs1_variant_assessment
PS3 No variant-specific functional evidence was identified. OncoKB classifies this variant as 'Unknown Oncogenic Effect' with no reviewed functional data. None of the reviewed publications reported functional studies on NM_133509.4:c.476G>A (p.Arg159His). Details ▾Hide ▴
Evidence considered
  • OncoKB: Unknown Oncogenic Effect
  • no variant-specific functional evidence
Still missing
  • Functional studies assessing homologous recombination activity of RAD51B p.Arg159His
Sources
oncokb ↗
PS4 No case-control or cohort studies reporting enrichment of NM_133509.4:c.476G>A in affected versus unaffected individuals were identified. The papers associated with this ClinVar entry are breast cancer screening guidelines, genetic testing policy statements, and BRCA1/BRCA2-focused studies that do not report RAD51B variant-specific prevalence data. Details ▾Hide ▴
Evidence considered
  • No variant-specific case-control data in any reviewed publication
  • ClinVar-associated papers are guidelines/policy statements
  • not case-level evidence
Still missing
  • Case-control study of RAD51B c.476G>A in breast/ovarian cancer cohorts
PM1 This variant (p.Arg159His) is not located in a statistically significant mutational hotspot and does not lie within a well-established critical functional domain with supporting literature evidence for missense constraint. Residue-level hotspot analysis returned negative. Details ▾Hide ▴
Evidence considered
  • Hotspot analysis: residue not significant
  • exact variant not listed in known hotspot
Still missing
  • Domain-level analysis of RAD51B functional domains and known pathogenic missense clusters
PM2 This variant is present in gnomAD v2.1 at an overall allele frequency of 0.042% (118/281,876 alleles) and in the South Asian subpopulation at 0.358% (109/30,430 alleles), exceeding the PM2 threshold of <0.1%. One homozygote is observed in gnomAD v2.1 and three homozygotes in gnomAD v4.1 (total AF=0.024%, 384/1,608,480 alleles, SAS AF=0.337%). The variant is too common in population databases to support PM2 for a presumed dominant disorder. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: AF=0.042%
  • SAS AF=0.358%
  • 1 homozygote
  • gnomAD v4.1: AF=0.024%
  • SAS AF=0.337%
  • 3 homozygotes
Sources
gnomad_v2 ↗gnomad_v4 ↗
PP3 Multiple in silico tools predict a benign impact for this variant. REVEL score is 0.385 (below the 0.5 damaging threshold), BayesDel score is 0.129 (low/near-zero), and SpliceAI predicts no splice impact (max delta score = 0.00). All computational lines of evidence argue against a damaging effect. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.385 (benign-leaning
  • below 0.5 threshold)
  • BayesDel: 0.129 (low
  • near-zero)
  • SpliceAI: max delta 0.00 (no splice impact)
Sources
revelbayesdelspliceai ↗
PP5 ClinVar reports this variant as Likely benign (3 clinical laboratories; ClinVar Variation ID 1678949), not pathogenic. PP5 requires a reputable source to have reported the variant as pathogenic. The ClinVar consensus classification does not support PP5. Details ▾Hide ▴
Evidence considered
  • ClinVar: Likely benign from 3 clinical laboratories (Ambry Genetics
  • PreventionGenetics
  • NHLS)
Sources
clinvar ↗
BA1 The overall allele frequency in gnomAD v2.1 is 0.042% and in gnomAD v4.1 is 0.024%, both well below the BA1 threshold of >1%. The highest subpopulation frequency (South Asian) is 0.358%, which also does not reach the 1% BA1 cutoff. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: overall AF=0.042%
  • max SAS AF=0.358%
  • gnomAD v4.1: overall AF=0.024%
  • max SAS AF=0.337%
Sources
gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 12 · no assessment recorded

PS1 No evidence that the same amino acid change (p.Arg159His) has been previously established as pathogenic via a different nucleotide change. No comparators identified in ClinVar or literature. Details ▾Hide ▴
Evidence considered
  • No same-amino-acid pathogenic variant identified in ClinVar or literature
Still missing
  • Database search for alternative nucleotide changes producing p.Arg159His with pathogenic classification
PS2 No de novo reports for NM_133509.4:c.476G>A were identified in ClinVar submissions, literature, or public databases. Details ▾Hide ▴
Evidence considered
  • No de novo evidence in ClinVar submissions or reviewed literature
Still missing
  • De novo testing of parental samples if clinically indicated
PM6 No de novo evidence for NM_133509.4:c.476G>A was identified. Without confirmed parental testing, PM6 cannot be applied. Details ▾Hide ▴
Evidence considered
  • No de novo reports in ClinVar or literature
Still missing
  • Parental testing if available
PP1 No segregation data for NM_133509.4:c.476G>A were identified in any reviewed publication or database. Details ▾Hide ▴
Evidence considered
  • No segregation data in ClinVar submissions or reviewed literature
Still missing
  • Family segregation analysis if affected relatives available
PP2 PP2 requires a low rate of benign missense variation in the gene and missense variants as a common disease mechanism. RAD51B germline disease appears primarily driven by truncating/LoF variants (PMID:25600502). Without gene-level missense constraint metrics (e.g., gnomAD Z-score, missense depletion data), PP2 cannot be confidently applied. Details ▾Hide ▴
Evidence considered
  • RAD51B disease mechanism: primarily LoF/truncating per PVS1 gene context
Still missing
  • gnomAD missense constraint Z-score for RAD51B
PP4 Patient-specific phenotype and family history data were not provided for this assessment. PP4 requires that the variant is identified in a patient whose phenotype or family history is highly specific for the gene-associated disease. Details ▾Hide ▴
Evidence considered
  • No patient-specific data available for assessment
Still missing
  • Patient phenotype and family history details
BS2 While this variant is observed in population databases (gnomAD), BS2 requires observation in a healthy adult individual for a disorder expected to be fully penetrant at an early age. RAD51B-associated cancer predisposition has incomplete and age-dependent penetrance, making BS2 difficult to apply without specific clinical data on the homozygous individuals observed in gnomAD. Details ▾Hide ▴
Evidence considered
  • gnomAD: 1 homozygote in v2.1
  • 3 homozygotes in v4.1
Still missing
  • Clinical status and age of gnomAD homozygous individuals
  • RAD51B penetrance data
BS3 No functional studies specifically assessing the impact of NM_133509.4:c.476G>A (p.Arg159His) on RAD51B protein function were identified. OncoKB reports no variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
  • OncoKB: no variant-specific functional data
Still missing
  • Functional studies (e.g.
  • homologous recombination assay) for RAD51B p.Arg159His
Sources
oncokb ↗
BS4 No segregation data for NM_133509.4:c.476G>A were identified in any reviewed publication. BS4 requires lack of segregation in affected family members. Details ▾Hide ▴
Evidence considered
  • No segregation data available
Still missing
  • Family segregation analysis
BP1 BP1 requires that the gene has a disease mechanism primarily through truncating variants and that the specific missense variant is in a gene where missense changes are not a known cause of disease. While RAD51B germline disease is associated with truncating mutations (PMID:25600502), insufficient evidence is available to determine whether pathogenic missense variants are absent from or rare in RAD51B. Details ▾Hide ▴
Evidence considered
  • RAD51B: truncating germline mutation reported (PMID:25600502)
  • No systematic missense constraint data available
Still missing
  • RAD51B missense constraint metrics
  • ClinVar curation of RAD51B missense variants
BP2 No data on observation of NM_133509.4:c.476G>A in trans with a known pathogenic RAD51B variant. BP2 is typically applied for recessive disorders. Details ▾Hide ▴
Evidence considered
  • No trans-phase data available
Still missing
  • Phasing data if additional RAD51B variants are identified
BP5 No data identifying an alternate molecular basis for disease in a case harboring NM_133509.4:c.476G>A was identified. Details ▾Hide ▴
Evidence considered
  • No alternate molecular cause data available
Still missing
  • Comprehensive genetic testing results if patient tested for broader panel
Not applicable · 3· recorded as not applicable Show reasons ▾Hide reasons ▴
PM5 N/ANo same-residue pathogenic comparator variants (different amino acid change at p.Arg159) were identified. Automatic PM5 candidate harvesting was unable to confirm classic same-residue semantics. Details ▾Hide ▴
Evidence considered
  • PM5 candidates: 0 same-residue comparators found
Still missing
  • Manual ClinVar search for pathogenic missense variants at Arg159
Sources
pm5_candidates
BP7 N/ANM_133509.4:c.476G>A is a missense variant (p.Arg159His), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
  • Variant is missense (p.Arg159His)
  • not synonymous
PS5 N/APS5 is not a criterion in the generic ACMG/AMP 2015 framework (PMID:25741868). Not applicable in generic_acmg mode. Details ▾Hide ▴
Evidence considered
  • PS5 does not exist in generic ACMG/AMP 2015 criteria set
Sources
generic_acmg_combination_rules

Identifiers

Gene
RAD51B
Transcript
NM_133509.4
Coding (HGVS c.)
NM_133509.4:c.476G>A
Protein (HGVS p.)
NP_598193.2:p.(Arg159His)
GRCh38
chr14:67885892 G>A
GRCh37
chr14:68352609 G>A
ClinVar
1678949
COSMIC
COSV66846898

Gene diagram

Every interpreted variant in RAD51B, mapped onto the exon structure of NM_133509.4. Select a row to find it on the plot.

RAD51BNM_133509.4
Fetching transcript structure from UCSC…
gnomAD v4.1 384 / 1,608,480 alleles AF 0.000239 · 3 homozygotes · FAF 0.00306
gnomAD v2.1 118 / 281,876 alleles AF 0.000419 · 1 homozygotes · FAF 0.00304
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.00024 · 384 / 1,608,480 alleles · 3 hom · FAF 0.0031
South Asian305 / 90,530 0.00343 hom
Remaining individuals18 / 62,184 0.00029
Admixed American14 / 59,870 0.00023
Middle Eastern1 / 6,028 0.00017
European (non-Finnish)43 / 1,176,150 3.7e-05
European (Finnish)2 / 63,862 3.1e-05
East Asian1 / 44,766 2.2e-05
0 alternate alleles recorded in 3 other groups: Amish, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 0.00042 · 118 / 281,876 alleles · 1 hom · FAF 0.003
South Asian109 / 30,430 0.00361 hom
Remaining individuals2 / 7,188 0.00028
Admixed American4 / 35,218 0.00011
European (Finnish)2 / 25,080 8e-05
European (non-Finnish)1 / 128,786 7.8e-06
0 alternate alleles recorded in 3 other groups: African/African American, Ashkenazi Jewish, East Asian.

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.000238735; MAF= 0.02387%, 384/1608480 alleles, homozygotes = 3) and has highest observed frequency in the South Asian population (AF= 0.00336905; MAF= 0.33690%, 305/90530 alleles, homozygotes = 3); grpmax FAF= 0.00305752.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.000418624; MAF= 0.04186%, 118/281876 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00358199; MAF= 0.35820%, 109/30430 alleles, homozygotes = 1); grpmax FAF= 0.00303643.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0006515365403409708, 12/18418 alleles, homozygotes = 0).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat -23 bp
0.000
SpliceAI acceptor gainat +10 bp
0.000
SpliceAI donor lossat -198 bp
0.000
SpliceAI donor gainat -23 bp
0.000
Pangolin splice lossmagnitude shown
-0.010
Pangolin splice gain
0.000

Other predictors

REVEL
0.385
BayesDel
0.129

How the predictions were used

BP4 SupportingMultiple lines of computational evidence consistently predict no damaging effect: REVEL score 0.385 (below the published 0.5 threshold for pathogenicity), BayesDel score 0.129 (near-zero, consistent with benign impact), and SpliceAI max delta score 0.00 (no predicted splice alteration). All available in silico tools agree on a benign prediction. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.385 (below 0.5 damaging threshold
  • benign-leaning)
  • BayesDel: 0.129 (near-zero
  • likely benign)
  • SpliceAI: max delta 0.00 (no splice impact predicted)
Sources
revelbayesdelspliceai ↗
PP3 Multiple in silico tools predict a benign impact for this variant. REVEL score is 0.385 (below the 0.5 damaging threshold), BayesDel score is 0.129 (low/near-zero), and SpliceAI predicts no splice impact (max delta score = 0.00). All computational lines of evidence argue against a damaging effect. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.385 (benign-leaning
  • below 0.5 threshold)
  • BayesDel: 0.129 (low
  • near-zero)
  • SpliceAI: max delta 0.00 (no splice impact)
Sources
revelbayesdelspliceai ↗
BP7 N/ANM_133509.4:c.476G>A is a missense variant (p.Arg159His), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
  • Variant is missense (p.Arg159His)
  • not synonymous

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.385. BayesDel score = 0.129411.

6 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

  • Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
    Phillips KA et al. · 2013
    Prospective cohort study examining whether adjuvant tamoxifen reduces contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. Does not discuss RAD51B or the variant NM_133509.4:c.476G>A.
    Does not name this variant
    PMID 23918944 ↗
  • Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
    ACMG/AMP 2015 standards and guidelines for the interpretation of sequence variants. This is the foundational methodological framework document used for variant classification, not a study reporting on any specific RAD51B variant.
    Does not name this variant
    PMID 25741868 ↗
  • American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.
    Saslow D et al. · 2007
    American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography, based on risk stratification (BRCA mutation carriers, lifetime risk >20-25%). Does not discuss RAD51B or any specific RAD51B variant.
    Does not name this variant
    PMID 17392385 ↗
  • BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.
    Adam MP et al. · 1993
    GeneReviews clinical summary of BRCA1- and BRCA2-associated hereditary breast and ovarian cancer. Discusses BRCA1/BRCA2 genes only; does not address RAD51B or NM_133509.4:c.476G>A.
    Does not name this variant
    PMID 20301425 ↗
  • ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.
    Green RC et al. · 2013
    ACMG 2013 recommendations for reporting incidental findings in clinical exome and genome sequencing, proposing a minimum list of genes to report. Does not discuss RAD51B or any specific RAD51B variant.
    Does not name this variant
    PMID 23788249 ↗
  • American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.
    ASCO 2015 policy statement update on genetic and genomic testing for cancer susceptibility. Provides clinical guidance on cancer genetic testing; does not report on any specific RAD51B variant.
    Does not name this variant
    PMID 26324357 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 384 / 1,608,480 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗
ClinVar 3 Likely benign Open source ↗
COSMIC Captured COSMIC source record Open source ↗
Cancer hotspots Captured Cancer Hotspots source record Open source ↗
OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.000238735; MAF= 0.02387%, 384/1608480 alleles, homozygotes = 3) and has highest observed frequency in the South Asian population (AF= 0.00336905; MAF= 0.33690%, 305/90530 alleles, homozygotes = 3); grpmax FAF= 0.00305752.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.000418624; MAF= 0.04186%, 118/281876 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00358199; MAF= 0.35820%, 109/30430 alleles, homozygotes = 1); grpmax FAF= 0.00303643.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0006515365403409708, 12/18418 alleles, homozygotes = 0).

ClinVar

This variant has been reported in ClinVar as Likely benign (3 clinical laboratories). (ClinVarID = 1678949)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.385. BayesDel score = 0.129411.

Functional

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. RAD51B, a DNA repair protein involved in homologous recombination, is altered by mutation in various cancer types.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV66846898, n = 2 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.