About RAD51B
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
RAD51B c.226G>A, p.(Ala76Thr)
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.
Words with a dotted underline have a short definition. Hover or tap them.
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
BS1Strong
BS1 · strong
The gnomAD v4.1 grpmax filtering allele frequency is 0.89%, exceeding the 0.3% BS1 threshold for generic non-VCEP ACMG adjudication. The Middle Eastern subpopulation allele frequency is 1.11% with 1 homozygote. In aggregate across v4.1, 2 homozygotes are observed in 1,613,538 alleles (621 total alleles). For a cancer predisposition gene where pathogenic variants are expected to be rare, this population frequency and the presence of homozygotes in ostensibly healthy population controls strongly supports a benign interpretation.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence consistently predict no impact on gene product: REVEL score 0.017 (well below 0.5 deleterious threshold), BayesDel score -0.558 (negative = benign), and SpliceAI max delta score 0.03 (no predicted splicing alteration). All available in silico tools concur in a benign assessment.
BP6Supporting
BP6 · supporting
Ambry Genetics, a reputable clinical diagnostic laboratory, has classified this variant as Likely benign with criteria provided (ClinVar accession SCV005488250). While the review status is 'criteria provided, single submitter' and not an expert panel consensus, the classification from a clinical testing laboratory with established variant interpretation practices 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 strong benign, BP4 supporting benign, BP6 supporting benign; combination = 1 strong benign + 2 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
621 / 1,613,538 alleles
gnomAD v4.1: 621 / 1,613,538 alleles. Recorded AF 0.000384869. Recorded homozygote count 2.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000424385; MAF= 0.04244%, 120/282762 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00110834; MAF= 0.11083%, 8/7218 alleles, homozygotes = 0); grpmax FAF= 0.00070522.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0011943539630836048, 22/18420 alleles, homozygotes = 0).
SpliceAI score
0.030 maximum delta
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
2 reported laboratory submissions
1 Uncertain significance · 1 Likely benign.
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
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV66842132, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
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 · 16 not met · 2 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_133509.4:c.226G>A (p.Ala76Thr) is a missense variant in exon 4 of RAD51B that is present in gnomAD v4.1 at a grpmax filtering allele frequency of 0.89%, exceeding the BS1 threshold of 0.3%, with 2 homozygotes observed in the general population.
Multiple in silico predictors consistently indicate a benign effect for this amino acid substitution: REVEL score 0.017, BayesDel score -0.558, and SpliceAI max delta 0.03, meeting BP4 at supporting benign strength.
Ambry Genetics, a clinical diagnostic laboratory, has classified this variant as Likely benign (ClinVar SCV005488250, criteria provided), meeting BP6 at supporting benign strength.
No pathogenic criteria are met. PVS1 is not applicable as the variant is missense. PS1-PS4, PM1-PM2, PM6, PP1-PP5, BS3-BS4, and BP1-BP2 are either not met or not applicable.
No criteria match.
Met · 3
BS1 StrongThe gnomAD v4.1 grpmax filtering allele frequency is 0.89%, exceeding the 0.3% BS1 threshold for generic non-VCEP ACMG adjudication. The Middle Eastern subpopulation allele frequency is 1.11% with 1 homozygote. In aggregate across v4.1, 2 homozygotes are observed in 1,613,538 alleles (621 total alleles). For a cancer predisposition gene where pathogenic variants are expected to be rare, this population frequency and the presence of homozygotes in ostensibly healthy population controls strongly supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF 0.89% (>0.3% BS1 threshold)
- Middle Eastern subpopulation AF 1.11% with 1 homozygote
- South Asian subpopulation AF 0.107% with 1 homozygote
- 2 total homozygotes in gnomAD v4.1
- 621 total alleles observed across 1
- 613
- 538 alleles.
Sources
BP4 SupportingMultiple lines of computational evidence consistently predict no impact on gene product: REVEL score 0.017 (well below 0.5 deleterious threshold), BayesDel score -0.558 (negative = benign), and SpliceAI max delta score 0.03 (no predicted splicing alteration). All available in silico tools concur in a benign assessment. Details ▾Hide ▴
Evidence considered
- REVEL 0.017 (benign)
- BayesDel -0.558 (benign)
- SpliceAI max delta 0.03 (no splice impact).
Sources
BP6 SupportingAmbry Genetics, a reputable clinical diagnostic laboratory, has classified this variant as Likely benign with criteria provided (ClinVar accession SCV005488250). While the review status is 'criteria provided, single submitter' and not an expert panel consensus, the classification from a clinical testing laboratory with established variant interpretation practices supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- ClinVar SCV005488250: Ambry Genetics classifies as Likely benign (criteria provided
- clinical testing).
Sources
Not met · 16 · evaluated, threshold not reached
PS1 No previously established pathogenic variant resulting in the same amino acid change (p.Ala76Thr) has been identified in ClinVar or the literature. The variant has not been classified as pathogenic by any submitter. Details ▾Hide ▴
Evidence considered
- ClinVar ID 584552 shows no pathogenic submissions for this amino acid change
- PM5 candidate search found no same-residue comparator variants.
Sources
clinvar ↗pm5_candidates
PS2 No de novo occurrence with confirmed paternity and maternity has been reported for this variant in the available literature or ClinVar submissions. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar submissions or literature_pass papers.
Still missing
- No family studies available for de novo assessment.
Sources
PS3 No well-established functional studies demonstrating a damaging effect have been identified for this variant. In silico predictors (REVEL 0.017, BayesDel -0.558) consistently suggest a benign effect. OncoKB lists the variant as 'Unknown Oncogenic Effect' with no curated functional evidence. Details ▾Hide ▴
Evidence considered
- REVEL score 0.017 (benign-leaning)
- BayesDel score -0.558 (benign-leaning)
- OncoKB reports no variant-specific functional evidence.
Still missing
- No dedicated functional studies for p.Ala76Thr in RAD51B.
Sources
PS4 No case-control or cohort data demonstrating statistically significant enrichment of this variant in affected individuals versus controls has been identified. The variant is observed in population databases at frequencies inconsistent with a rare pathogenic variant. Details ▾Hide ▴
Evidence considered
- No case-control enrichment data available
- ClinVar reports only 2 germline submissions (1 VUS
- 1 Likely benign)
- variant present in gnomAD at 0.038% with 2 homozygotes.
Still missing
- No case-control studies available for RAD51B p.Ala76Thr.
Sources
PM1 Residue Ala76 does not lie within a statistically significant mutational hotspot in RAD51B, nor within a well-established critical functional domain defined by a RAD51B-specific VCEP framework. The hotspot analysis did not identify this position as significant. Details ▾Hide ▴
Evidence considered
- Hotspot assessment negative
- residue Ala76 not listed in any statistically significant hotspot
- no VCEP-defined functional domains for RAD51B.
Still missing
- No RAD51B-specific functional domain map available for PM1 adjudication.
PM2 Although the overall allele frequency in gnomAD v2.1 (0.042%) and v4.1 (0.038%) is below the 0.1% PM2 threshold, gnomAD v4.1 reports 2 homozygotes and a grpmax filtering allele frequency of 0.89% (>0.3% BS1 threshold). The presence of homozygotes in a population database for a cancer predisposition gene contradicts the expectation that a pathogenic variant would be absent or extremely rare, and the elevated grpmax FAF exceeds the BS1 cutoff, further undermining PM2 applicability. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 120/282762 alleles (0.042%)
- 0 homozygotes
- gnomAD v4.1: 621/1613538 alleles (0.038%)
- 2 homozygotes
- grpmax FAF 0.89%
- Middle Eastern subpopulation AF 1.11% with 1 homozygote.
Sources
PM6 No de novo occurrence (without confirmed paternity and maternity) has been reported for this variant in ClinVar submissions or the available literature. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar submissions
- no literature evidence of de novo occurrence for RAD51B p.Ala76Thr.
Still missing
- No family studies available for de novo assessment.
Sources
PP1 No co-segregation data with disease in multiple affected family members is available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation studies or family pedigrees found for RAD51B p.Ala76Thr.
Still missing
- No family segregation data available.
PP3 Multiple in silico predictors consistently indicate a benign effect: REVEL score 0.017 (well below the 0.5 threshold for deleterious prediction), BayesDel score -0.558 (negative = benign), and SpliceAI max delta 0.03 (no predicted splicing impact). No computational tool supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL 0.017 (benign)
- BayesDel -0.558 (benign)
- SpliceAI max delta 0.03 (no splice impact).
Sources
PP5 No reputable source has classified this variant as pathogenic. ClinVar reports one submission as Uncertain significance (GeneKor MSA) and one as Likely benign (Ambry Genetics). Neither submission is from an expert panel, and the only classification from a clinical testing laboratory with criteria provided is Likely benign. Details ▾Hide ▴
Evidence considered
- ClinVar ID 584552: 1 VUS (GeneKor MSA
- criteria provided)
- 1 Likely benign (Ambry Genetics
- criteria provided
- clinical testing). No expert panel or pathogenic classification.
Sources
BA1 The overall allele frequency in gnomAD v4.1 is 0.038%, and the highest subpopulation frequency (Middle Eastern) is 1.11%. Neither approaches the BA1 threshold of >5%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 overall AF 0.038%
- highest subpopulation AF 1.11% (Middle Eastern)
- BA1 requires >5%.
Sources
BS3 No well-established functional studies demonstrating no damaging effect have been identified for this variant. While in silico predictors are consistently benign, these are captured under BP4 and do not independently constitute BS3-level functional evidence. Details ▾Hide ▴
Evidence considered
- No dedicated functional assays (e.g.
- homology recombination assay
- protein interaction studies) performed for p.Ala76Thr.
Still missing
- No in vitro functional studies available for RAD51B p.Ala76Thr.
Sources
revelbayesdel
BS4 No family segregation data demonstrating lack of co-segregation with disease is available for this variant. Details ▾Hide ▴
Evidence considered
- No family studies or segregation data available for RAD51B p.Ala76Thr.
Still missing
- No segregation data available.
BP1 BP1 applies to missense variants in genes where only truncating variants are known to cause disease. While RAD51B loss-of-function via truncating variants is a reported disease mechanism (as confirmed in the PVS1 gene context), there is insufficient evidence to conclude that missense variants in RAD51B are never pathogenic. RAD51 paralogs (RAD51C, RAD51D) have both truncating and proven pathogenic missense variants, and the generic ACMG framework cannot confidently restrict RAD51B pathogenicity to truncating variants alone. Details ▾Hide ▴
Evidence considered
- RAD51B LoF mechanism supported by germline literature
- however
- missense variants in RAD51 paralog family members can be pathogenic
- insufficient evidence to apply BP1 in generic mode.
Still missing
- No VCEP guidance on whether RAD51B missense variants are excluded from pathogenicity.
Sources
pvs1_gene_context
BP2 No observation of this variant in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant for a recessive disorder, has been reported. Details ▾Hide ▴
Evidence considered
- No phase data or co-occurrence data available.
Still missing
- No phasing data or variant co-occurrence reports available.
BP5 No observation of this variant in a case where an alternate molecular basis for disease has been identified. Details ▾Hide ▴
Evidence considered
- No co-occurring pathogenic variant data or alternate molecular diagnosis reports available.
Still missing
- No data on alternate molecular diagnoses in carriers.
Not assessed · 2 · no assessment recorded
PP2 PP2 assessment requires gene-level constraint metrics (e.g., missense Z-score from gnomAD) to determine whether RAD51B has a low rate of benign missense variation and whether missense variants are a common mechanism of disease. These metrics are not available in the generic ACMG adjudication workflow for RAD51B. Details ▾Hide ▴
Evidence considered
- Gene constraint data (missense Z-score
- o/e ratio) not available in the evidence brief for RAD51B.
Still missing
- Requires manual retrieval of gnomAD gene constraint metrics for RAD51B to determine whether PP2 is applicable.
PP4 No patient phenotype or clinical history data are available for this variant. PP4 requires that the proband's phenotype or family history is highly specific for a disease with a single genetic etiology, which cannot be assessed without clinical data. Details ▾Hide ▴
Evidence considered
- No patient-level phenotype data available in the case materials.
Still missing
- Patient phenotype and family history not provided for PP4 adjudication.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_133509.4:c.226G>A is a missense variant (p.Ala76Thr) and does not fall into any default PVS1 null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice consensus). The generic PVS1 decision tree does not apply to this variant class. Details ▾Hide ▴
Evidence considered
- Missense substitution in exon 4
- not a predicted loss-of-function variant
- PVS1 framework explicitly excludes non-null variant types.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PM5 N/ANo same-residue pathogenic comparator variant at Ala76 was identified in ClinVar. The automated PM5 candidate search found no eligible variants for same-residue comparison. Details ▾Hide ▴
Evidence considered
- PM5 candidate report: no same-residue (p.Ala76) comparator variants with pathogenic classification found
- PM5 semantics could not be confirmed.
Sources
pm5_candidates
BS2 N/ABS2 requires observation in a healthy adult individual for a disorder with full penetrance expected at an early age. RAD51B-associated cancer predisposition has incomplete penetrance and adult onset, and therefore does not meet the strict BS2 criteria for early-onset, fully penetrant disorders. The observed homozygotes in gnomAD are captured under BS1 instead. Details ▾Hide ▴
Evidence considered
- BS2 is designed for early-onset
- fully penetrant disorders
- RAD51B cancer risk is moderate-penetrance
- adult-onset
- homozygote evidence is applied through BS1.
Sources
BP7 N/ANM_133509.4:c.226G>A is a missense variant (p.Ala76Thr) resulting in an amino acid substitution, not a synonymous variant. BP7 applies exclusively to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense (G>A at c.226
- resulting in p.Ala76Thr).
PS5 N/APS5 is not a standard criterion in the generic ACMG/AMP 2015 framework (PMID:25741868). No VCEP framework exists for RAD51B to define a custom PS5 rule. Details ▾Hide ▴
Evidence considered
- Generic ACMG/AMP 2015 does not include PS5
- no RAD51B VCEP framework available to define gene-specific criteria.
Sources
Identifiers
- Gene
- RAD51B
- Transcript
- NM_133509.4
- Coding (HGVS c.)
- NM_133509.4:c.226G>A
- Protein (HGVS p.)
- NP_598193.2:p.(Ala76Thr)
- GRCh38
- chr14:67835107 G>A
- GRCh37
- chr14:68301824 G>A
- ClinVar
- 584552
- COSMIC
- COSV66842132
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…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in RAD51B
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
621 / 1,613,538 alleles
AF 0.000385 · 2 homozygotes · FAF 0.00893
gnomAD v2.1
120 / 282,762 alleles
AF 0.000424 · 0 homozygotes · FAF 0.000705
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00038 · 621 / 1,613,538 alleles · 2 hom · FAF 0.0089
| Middle Eastern67 / 6,058 | 0.0111 hom |
| Admixed American80 / 59,992 | 0.0013 |
| South Asian97 / 91,058 | 0.00111 hom |
| Remaining individuals34 / 62,494 | 0.00054 |
| European (non-Finnish)326 / 1,179,564 | 0.00028 |
| African/African American15 / 74,990 | 0.0002 |
| Ashkenazi Jewish2 / 29,600 | 6.8e-05 |
0 alternate alleles recorded in 3 other groups: European (Finnish), Amish, East Asian.
gnomAD v2.1
AF 0.00042 · 120 / 282,762 alleles · 0 hom · FAF 0.00071
| Remaining individuals8 / 7,218 | 0.0011 |
| South Asian30 / 30,614 | 0.00098 |
| Admixed American27 / 35,404 | 0.00076 |
| European (non-Finnish)52 / 129,126 | 0.0004 |
| Ashkenazi Jewish3 / 10,368 | 0.00029 |
0 alternate alleles recorded in 3 other groups: African/African American, East Asian, European (Finnish).
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000384869; MAF= 0.03849%, 621/1613538 alleles, homozygotes = 2) and has highest observed frequency in the Middle Eastern population (AF= 0.0110598; MAF= 1.10598%, 67/6058 alleles, homozygotes = 1); grpmax FAF= 0.00893491.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000424385; MAF= 0.04244%, 120/282762 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00110834; MAF= 0.11083%, 8/7218 alleles, homozygotes = 0); grpmax FAF= 0.00070522.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0011943539630836048, 22/18420 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.017
- BayesDel
- -0.558
How the predictions were used
BP4 SupportingMultiple lines of computational evidence consistently predict no impact on gene product: REVEL score 0.017 (well below 0.5 deleterious threshold), BayesDel score -0.558 (negative = benign), and SpliceAI max delta score 0.03 (no predicted splicing alteration). All available in silico tools concur in a benign assessment. Details ▾Hide ▴
Evidence considered
- REVEL 0.017 (benign)
- BayesDel -0.558 (benign)
- SpliceAI max delta 0.03 (no splice impact).
Sources
PP3 Multiple in silico predictors consistently indicate a benign effect: REVEL score 0.017 (well below the 0.5 threshold for deleterious prediction), BayesDel score -0.558 (negative = benign), and SpliceAI max delta 0.03 (no predicted splicing impact). No computational tool supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL 0.017 (benign)
- BayesDel -0.558 (benign)
- SpliceAI max delta 0.03 (no splice impact).
Sources
BP7 N/ANM_133509.4:c.226G>A is a missense variant (p.Ala76Thr) resulting in an amino acid substitution, not a synonymous variant. BP7 applies exclusively to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense (G>A at c.226
- resulting in p.Ala76Thr).
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.017. BayesDel score = -0.557559.
2 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
-
PMID 25741868 ↗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.Richards S et al. · 2015Standards 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. This is a methodology guideline and does not mention any specific RAD51B variant.Does not name this variant
-
PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. This is a clinical practice guideline and does not mention any specific RAD51B variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
621 / 1,613,538 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.030
Open source ↗
ClinVar
1 Uncertain significance · 1 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
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/584552/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/14-68301824-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr14-67835107-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/14-67835107-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_133509.4%3Ac.226G…
- OncoKB ↗www.oncokb.org/gene/RAD51B/A76T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=172486972
- Cancer hotspots ↗www.cancerhotspots.org/
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= 0.000384869; MAF= 0.03849%, 621/1613538 alleles, homozygotes = 2) and has highest observed frequency in the Middle Eastern population (AF= 0.0110598; MAF= 1.10598%, 67/6058 alleles, homozygotes = 1); grpmax FAF= 0.00893491.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000424385; MAF= 0.04244%, 120/282762 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00110834; MAF= 0.11083%, 8/7218 alleles, homozygotes = 0); grpmax FAF= 0.00070522.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0011943539630836048, 22/18420 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratory) and as Likely benign (1 clinical laboratory). (ClinVarID = 584552)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.017. BayesDel score = -0.557559.
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; COSV66842132, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.