0%
RAD51Bc.481C>TLikely benign
Print report
Variant interpretation report

RAD51B c.481C>T, p.(Pro161Ser)

NM_133509.3:c.481C>T NP_598193.2:p.(Pro161Ser) 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: 1 Benign evidence criteria: 2
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

NM_133509.3:c.481C>T is absent from gnomAD v2.1 and gnomAD v4.1, meeting the generic ACMG PM2 threshold (allele frequency <0.1% in population databases).

Benign criteria applied · 2
BP1Supporting
BP1 · supporting

NM_133509.3:c.481C>T (p.Pro161Ser) is a missense variant in RAD51B, a gene for which the established disease mechanism is loss-of-function via truncating variants. The published literature documents germline nonsense and splice-site mutations as pathogenic, while missense variants are not a well-established disease mechanism for this gene (PMID:25600502, PMID:21533530).

BP4Supporting
BP4 · supporting

Multiple lines of computational evidence predict no impact on gene product: REVEL score 0.289 (below 0.5 threshold), BayesDel score -0.077 (negative score indicates benign), and SpliceAI max delta score 0.11 (below 0.2 threshold, no predicted splice alteration).

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: PM2 supporting, BP1 supporting benign, BP4 supporting benign; combination = 1 supporting + 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.

SpliceAI score
0.110 maximum delta

Recorded SpliceAI maximum delta score: 0.110. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗
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; COSV66849284, 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.

29 criteria with recorded statuses: 3 met · 21 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_133509.3:c.481C>T (p.Pro161Ser) is absent from gnomAD v2.1 and v4.1, meeting PM2 at supporting strength.

The variant is a missense change in RAD51B, a gene where the established disease mechanism is loss-of-function via truncating variants. Published germline RAD51B pathogenic variants are nonsense or splice-site mutations (PMID:25600502), and systematic screening of RAD51B found no pathogenic missense variants in breast cancer families (PMID:21533530). BP1 is met at supporting benign strength.

Multiple in silico tools predict a benign effect: REVEL score 0.289, BayesDel score -0.077, and SpliceAI max delta 0.11. BP4 is met at supporting benign strength.

The variant is absent from ClinVar; no classification or functional evidence exists for this variant in the literature. OncoKB reports unknown oncogenic effect, and COSMIC reports the variant in somatic cancers (n=2) without functional characterization.

Applying generic ACMG/AMP 2015 combination rules (PMID:25741868): with two supporting benign criteria (BP1, BP4) and one supporting pathogenic criterion (PM2), the evidence weighs in favor of a benign interpretation, meeting the threshold for Likely Benign.

Met · 3

PM2 SupportingNM_133509.3:c.481C>T is absent from gnomAD v2.1 and gnomAD v4.1, meeting the generic ACMG PM2 threshold (allele frequency <0.1% in population databases). Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1
  • v4.1
  • and gnomAD-Canada v1.0.
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BP1 SupportingNM_133509.3:c.481C>T (p.Pro161Ser) is a missense variant in RAD51B, a gene for which the established disease mechanism is loss-of-function via truncating variants. The published literature documents germline nonsense and splice-site mutations as pathogenic, while missense variants are not a well-established disease mechanism for this gene (PMID:25600502, PMID:21533530). Details ▾Hide ▴
Evidence considered
  • RAD51B disease mechanism is truncating LOF. PMID:25600502 reports a germline nonsense mutation as pathogenic. PMID:21533530 finds no truncating mutations and concludes RAD51B is unlikely a high-penetrance gene.
Sources
pvs1_gene_context
BP4 SupportingMultiple lines of computational evidence predict no impact on gene product: REVEL score 0.289 (below 0.5 threshold), BayesDel score -0.077 (negative score indicates benign), and SpliceAI max delta score 0.11 (below 0.2 threshold, no predicted splice alteration). Details ▾Hide ▴
Evidence considered
  • REVEL 0.289
  • BayesDel -0.077
  • SpliceAI max delta 0.11 — all three in silico tools predict a benign effect.
Sources
revelbayesdelspliceai ↗

Not met · 21 · evaluated, threshold not reached

PS1 No known pathogenic variant at codon 161 with the same amino acid change (p.Pro161Ser) has been identified. The variant is entirely absent from ClinVar. Details ▾Hide ▴
Evidence considered
  • No same-amino-acid pathogenic comparator in ClinVar.
Still missing
  • No ClinVar entries for any variant at codon 161 of RAD51B.
Sources
clinvar ↗
PS2 No de novo evidence is available. No family-based or parent-of-origin studies report this variant as a confirmed de novo occurrence. Details ▾Hide ▴
Evidence considered
  • No de novo data in case materials.
Still missing
  • No pedigree or parent testing data supplied.
PS3 No variant-specific functional studies were identified. OncoKB reports unknown oncogenic effect. REVEL (0.289) and BayesDel (-0.077) predict a benign effect. No published experimental data exist for p.Pro161Ser or a systematically characterized range that includes residue 161. Details ▾Hide ▴
Evidence considered
  • OncoKB: unknown oncogenic effect. REVEL 0.289
  • BayesDel -0.077 — both predict benign.
Still missing
  • No functional studies of RAD51B p.Pro161Ser or residue 161 range.
Sources
oncokb ↗revelbayesdel
PS4 No case-control or cohort prevalence data are available. Variant is absent from ClinVar and has not been reported in affected individuals in the curated literature. Details ▾Hide ▴
Evidence considered
  • Variant absent from ClinVar and gnomAD
  • no case counts available.
Still missing
  • No published case series reporting this variant.
Sources
clinvar ↗gnomad_v2 ↗gnomad_v4 ↗
PM1 Residue 161 (Pro) is not located in a statistically significant mutational hotspot per cancerhotspots.org. No domain-level functional characterization data identifying this residue as critical was found in the case materials. Details ▾Hide ▴
Evidence considered
  • cancerhotspots.org: residue 161 is not in a statistically significant hotspot.
Still missing
  • No domain-level data for RAD51B residue 161 in case materials.
PM5 No pathogenic missense variant at codon 161 of RAD51B was identified in ClinVar. Automated PM5 candidate harvesting returned no same-codon comparator variants. Details ▾Hide ▴
Evidence considered
  • No same-codon pathogenic missense comparators found.
Still missing
  • No ClinVar entries for any missense change at RAD51B codon 161.
Sources
pm5_candidatesclinvar ↗
PM6 No assumed de novo evidence is available. No reports of this variant occurring de novo without confirmed parentage. Details ▾Hide ▴
Evidence considered
  • No de novo reports in case materials.
Still missing
  • No de novo or parentage data supplied.
PP1 No co-segregation data are available. No family-based studies with this variant. Details ▾Hide ▴
Evidence considered
  • No segregation data in case materials.
Still missing
  • No pedigree or co-segregation data supplied.
PP2 RAD51B disease mechanism is loss-of-function via truncating variants; missense variation is not a well-established disease mechanism for this gene. Additionally, no missense constraint data (HCI prior not available for RAD51B) exists to support a low rate of benign missense variation. Details ▾Hide ▴
Evidence considered
  • RAD51B established mechanism is truncating LOF (PMID:25600502
  • PMID:21533530). HCI prior not found for RAD51B.
Still missing
  • No missense constraint metrics available for RAD51B.
Sources
pvs1_gene_context
PP3 Multiple in silico tools predict a benign effect: REVEL score 0.289 (below 0.5 threshold), BayesDel score -0.077 (negative score indicates benign), SpliceAI max delta 0.11 (below 0.2 threshold). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
  • REVEL 0.289
  • BayesDel -0.077
  • SpliceAI max delta 0.11 — all predict benign.
Sources
revelbayesdelspliceai ↗
PP4 No patient phenotype or clinical history was provided. Cannot assess whether the phenotype is highly specific for RAD51B-related disease. Details ▾Hide ▴
Evidence considered
  • No clinical phenotype data in case materials.
Still missing
  • No patient phenotype or clinical data supplied.
PP5 The variant is absent from ClinVar. No reputable source has classified NM_133509.3:c.481C>T as pathogenic. Details ▾Hide ▴
Evidence considered
  • Not present in ClinVar
  • no expert panel or submitter classification exists.
Still missing
  • No ClinVar classification.
Sources
clinvar ↗
BA1 Variant is absent from gnomAD v2.1 and v4.1. Allele frequency does not exceed the 1% BA1 threshold in any population. Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD
  • frequency is 0%.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 Variant is absent from gnomAD. Population allele frequency does not exceed the 0.3% BS1 threshold. Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD
  • frequency is 0%.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 No data on observation in healthy adult controls or unaffected individuals are available. Details ▾Hide ▴
Evidence considered
  • No healthy control observation data in case materials.
Still missing
  • No control cohort data available.
BS3 No well-established in vitro or in vivo functional studies demonstrate no damaging effect for p.Pro161Ser. While in silico tools predict benign, this alone does not satisfy BS3 which requires experimental functional evidence. Details ▾Hide ▴
Evidence considered
  • No experimental functional studies available
  • in silico predictions alone insufficient for BS3.
Still missing
  • No experimental functional data for p.Pro161Ser.
Sources
revelbayesdel
BS4 No segregation data are available to demonstrate lack of co-segregation with disease in affected family members. Details ▾Hide ▴
Evidence considered
  • No segregation data in case materials.
Still missing
  • No pedigree or segregation data.
BP2 No phasing data are available. Cannot assess whether this variant has been observed in trans with a pathogenic variant in RAD51B. Details ▾Hide ▴
Evidence considered
  • No phasing or trans data in case materials.
Still missing
  • No phasing or allelic data available.
BP5 No information about an alternate molecular basis for disease in this case is available. Details ▾Hide ▴
Evidence considered
  • No alternate molecular diagnosis data provided.
Still missing
  • No alternate molecular basis data.
BP6 The variant is absent from ClinVar. No reputable source has classified this variant as benign. Details ▾Hide ▴
Evidence considered
  • No ClinVar classification exists
  • variant is absent from ClinVar.
Still missing
  • No ClinVar benign classification.
Sources
clinvar ↗
PS5 Variant is absent from ClinVar; no reputable source has classified NM_133509.3:c.481C>T as pathogenic. Details ▾Hide ▴
Evidence considered
  • Not present in ClinVar.
Still missing
  • No ClinVar classification exists for this variant.
Sources
clinvar ↗
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/Ac.481C>T is a missense variant producing p.Pro161Ser. This does not fall into the generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
  • Missense substitution does not meet PVS1 null-variant criteria.
Sources
pvs1_generic_framework ↗
PM3 N/ABiallelic/recessive criterion; no phasing data available and RAD51B-related disease is not established as autosomal recessive. Details ▾Hide ▴

No further detail was recorded.

PM4 N/AProtein length change criterion (non-repeat region); this variant is a single-nucleotide substitution, not an in-frame deletion/insertion or stop-loss. Details ▾Hide ▴

No further detail was recorded.

BP3 N/AIn-frame deletion/insertion criterion; this variant is a single-nucleotide substitution. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ABP7 applies to synonymous (silent) variants. NM_133509.3:c.481C>T is a missense variant producing p.Pro161Ser. Details ▾Hide ▴
Evidence considered
  • Missense variant is outside the scope of BP7.

Identifiers

Gene
RAD51B
Transcript
NM_133509.3
Coding (HGVS c.)
NM_133509.3:c.481C>T
Protein (HGVS p.)
NP_598193.2:p.(Pro161Ser)
GRCh38
chr14:67885897 C>T
GRCh37
chr14:68352614 C>T
COSMIC
COSV66849284

Gene diagram

Every interpreted variant in RAD51B, mapped onto the exon structure of NM_133509.3. Select a row to find it on the plot.

RAD51BNM_133509.3
Fetching transcript structure from UCSC…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -28 bp
0.000
SpliceAI acceptor gainat +5 bp
0.110
SpliceAI donor lossat +91 bp
0.000
SpliceAI donor gainat +5 bp
0.000
Pangolin splice lossmagnitude shown
-0.010
Pangolin splice gain
0.050

Other predictors

REVEL
0.289
BayesDel
-0.077

How the predictions were used

BP4 SupportingMultiple lines of computational evidence predict no impact on gene product: REVEL score 0.289 (below 0.5 threshold), BayesDel score -0.077 (negative score indicates benign), and SpliceAI max delta score 0.11 (below 0.2 threshold, no predicted splice alteration). Details ▾Hide ▴
Evidence considered
  • REVEL 0.289
  • BayesDel -0.077
  • SpliceAI max delta 0.11 — all three in silico tools predict a benign effect.
Sources
revelbayesdelspliceai ↗
PP3 Multiple in silico tools predict a benign effect: REVEL score 0.289 (below 0.5 threshold), BayesDel score -0.077 (negative score indicates benign), SpliceAI max delta 0.11 (below 0.2 threshold). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
  • REVEL 0.289
  • BayesDel -0.077
  • SpliceAI max delta 0.11 — all predict benign.
Sources
revelbayesdelspliceai ↗
BP7 N/ABP7 applies to synonymous (silent) variants. NM_133509.3:c.481C>T is a missense variant producing p.Pro161Ser. Details ▾Hide ▴
Evidence considered
  • Missense variant is outside the scope of BP7.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.11). REVEL score = 0.289. BayesDel score = -0.0772252.

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

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

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.110 Open source ↗
ClinVar Captured ClinVar source record 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

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant is absent from ClinVar.

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.11). REVEL score = 0.289. BayesDel score = -0.0772252.

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; COSV66849284, n = 2 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.