dbSNP rs17829444: RAD51B:c.1037-6124G>A (chr14-68604882-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001321821.2(RAD51B):c.1037-6124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,062 control chromosomes in the GnomAD database, including 2,434 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2434 hom., cov: 32)

Consequence

RAD51B
NM_001321821.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138

Publications

2 publications found

Variant links:

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B Gene-Disease associations (from GenCC):

primary ovarian failure
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RAD51B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321821.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-6124G>A	intron	N/A	NP_001308750.1	C9JYJ0
RAD51B	NM_001321809.2	c.*33+2179G>A	intron	N/A	NP_001308738.1
RAD51B	NM_001321818.2	c.1037-78055G>A	intron	N/A	NP_001308747.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD51B	ENST00000487861.5	TSL:1	c.1037-6124G>A	intron	N/A	ENSP00000419881.1	C9JYJ0
RAD51B	ENST00000488612.5	TSL:1	c.1037-45899G>A	intron	N/A	ENSP00000420061.1	O15315-4
RAD51B	ENST00000478014.5	TSL:3	n.384-78055G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26184

AN:

151944

Hom.:

2432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.172

AC:

26205

AN:

152062

Hom.:

2434

Cov.:

AF XY:

0.171

AC XY:

12725

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.119

AC:

4931

AN:

41484

American (AMR)

AF:

0.140

AC:

2145

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

529

AN:

3468

East Asian (EAS)

AF:

0.143

AC:

738

AN:

5170

South Asian (SAS)

AF:

0.101

AC:

488

AN:

4818

European-Finnish (FIN)

AF:

0.246

AC:

2599

AN:

10552

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14107

AN:

67976

Other (OTH)

AF:

0.164

AC:

346

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1107

2213

3320

4426

5533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.191

Hom.:

11607

Bravo

AF:

0.163

Asia WGS

AF:

0.116

AC:

401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.8

(source)

DANN

Benign

0.79

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over