Genetic Variant ENST00000487270.5:c.*1003G>A (chr14-68595606-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000487270.5(RAD51B):c.*1003G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,064,476 control chromosomes in the GnomAD database, including 50,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 6112 hom., cov: 32)

Exomes 𝑓: 0.31 ( 44281 hom. )

Consequence

RAD51B
ENST00000487270.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.321

Publications

16 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 14-68595606-G-A is Benign according to our data. Variant chr14-68595606-G-A is described in ClinVar as [Benign]. Clinvar id is 4077038.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
RAD51B	NM_133509.5 link	c.*1003G>A	3_prime_UTR_variant	Exon 11 of 11	NP_598193.2	O15315-3
RAD51B	NM_001321821.2 link	c.1037-15400G>A	intron_variant	Intron 10 of 10	NP_001308750.1	C9JYJ0
RAD51B	NM_001321809.2 link	c.1037-7057G>A	intron_variant	Intron 10 of 11	NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
RAD51B	ENST00000487270.5 link	c.*1003G>A	3_prime_UTR_variant	Exon 11 of 11	1	ENSP00000419471.1	O15315-3
RAD51B	ENST00000487861.5 link	c.1037-15400G>A	intron_variant	Intron 10 of 10	1	ENSP00000419881.1	C9JYJ0
RAD51B	ENST00000488612.5 link	c.1037-55175G>A	intron_variant	Intron 10 of 11	1	ENSP00000420061.1	O15315-4

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40572

AN:

151944

Hom.:

6113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.308

AC:

280858

AN:

912414

Hom.:

44281

Cov.:

AF XY:

0.308

AC XY:

129656

AN XY:

421220

show subpopulations

African (AFR)

AF:

0.109

AC:

2136

AN:

19658

American (AMR)

AF:

0.294

AC:

1021

AN:

3478

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

2112

AN:

10260

East Asian (EAS)

AF:

0.488

AC:

7299

AN:

14972

South Asian (SAS)

AF:

0.343

AC:

5877

AN:

17124

European-Finnish (FIN)

AF:

0.347

AC:

264

AN:

760

Middle Eastern (MID)

AF:

0.241

AC:

507

AN:

2102

European-Non Finnish (NFE)

AF:

0.310

AC:

251487

AN:

810048

Other (OTH)

AF:

0.299

AC:

10155

AN:

34012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9068

18136

27204

36272

45340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.267

AC:

40572

AN:

152062

Hom.:

6112

Cov.:

AF XY:

0.273

AC XY:

20273

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.123

AC:

5115

AN:

41484

American (AMR)

AF:

0.301

AC:

4601

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

711

AN:

3468

East Asian (EAS)

AF:

0.508

AC:

2630

AN:

5176

South Asian (SAS)

AF:

0.353

AC:

1701

AN:

4820

European-Finnish (FIN)

AF:

0.368

AC:

3886

AN:

10554

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

21023

AN:

67982

Other (OTH)

AF:

0.273

AC:

577

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1461

2921

4382

5842

7303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.295

Hom.:

16906

Bravo

AF:

0.257

Asia WGS

AF:

0.411

AC:

1427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.4

(source)

DANN

Benign

0.70

PhyloP100

0.32

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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ENST00000487270.5:c.*1003G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over