dbSNP rs961700: RAD51B:c.316-283G>A (chr14-67864720-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133510.4(RAD51B):c.316-283G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 522,082 control chromosomes in the GnomAD database, including 38,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13552 hom., cov: 32)

Exomes 𝑓: 0.35 ( 25002 hom. )

Consequence

RAD51B
NM_133510.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0130

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-67864720-G-A is Benign according to our data. Variant chr14-67864720-G-A is described in ClinVar as Benign. ClinVar VariationId is 1183458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4 link	c.316-283G>A		intron_variant	Intron 4 of 10	ENST00000471583.6	NP_598194.1	O15315-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6 link	c.316-283G>A		intron_variant	Intron 4 of 10	1	NM_133510.4	ENSP00000418859.1		O15315-2

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61668

AN:

151844

Hom.:

13526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.542

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.0755

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.410

GnomAD4 exome

AF:

0.353

AC:

130794

AN:

370120

Hom.:

25002

AF XY:

0.347

AC XY:

71594

AN XY:

206064

show subpopulations

African (AFR)

AF:

0.558

AC:

6350

AN:

11380

American (AMR)

AF:

0.238

AC:

6567

AN:

27630

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

6085

AN:

13648

East Asian (EAS)

AF:

0.0867

AC:

1279

AN:

14760

South Asian (SAS)

AF:

0.261

AC:

15244

AN:

58452

European-Finnish (FIN)

AF:

0.326

AC:

4676

AN:

14334

Middle Eastern (MID)

AF:

0.436

AC:

1372

AN:

3144

European-Non Finnish (NFE)

AF:

0.394

AC:

82001

AN:

207878

Other (OTH)

AF:

0.382

AC:

7220

AN:

18894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

3701

7402

11103

14804

18505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

570

1140

1710

2280

2850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.406

AC:

61738

AN:

151962

Hom.:

13552

Cov.:

AF XY:

0.397

AC XY:

29539

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.542

AC:

22474

AN:

41428

American (AMR)

AF:

0.316

AC:

4819

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

1567

AN:

3464

East Asian (EAS)

AF:

0.0759

AC:

393

AN:

5178

South Asian (SAS)

AF:

0.268

AC:

1294

AN:

4822

European-Finnish (FIN)

AF:

0.311

AC:

3278

AN:

10544

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.392

AC:

26626

AN:

67960

Other (OTH)

AF:

0.404

AC:

854

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1800

3601

5401

7202

9002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.393

Hom.:

32087

Bravo

AF:

0.411

Asia WGS

AF:

0.204

AC:

711

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

(source)

DANN

Benign

0.81

PhyloP100

0.013

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over