dbSNP rs17105852: RAD51B:c.1037-47071C>A (chr14-68563935-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000487861.5(RAD51B):c.1037-47071C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 982,132 control chromosomes in the GnomAD database, including 648 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 0.044 ( 180 hom., cov: 33)

Exomes 𝑓: 0.032 ( 468 hom. )

Consequence

RAD51B
ENST00000487861.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.184

Publications

11 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:

LOC124903335 (HGNC:):

LOC124903335 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
LOC124903335	XR_007064224.1 link	n.1316G>T	non_coding_transcript_exon_variant	Exon 1 of 2
LOC124903335	XR_007064226.1 link	n.1316G>T	non_coding_transcript_exon_variant	Exon 1 of 3
RAD51B	NM_001321821.2 link	c.1037-47071C>A	intron_variant	Intron 10 of 10	NP_001308750.1	C9JYJ0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
RAD51B	ENST00000487861.5 link	c.1037-47071C>A	intron_variant	Intron 10 of 10	1	ENSP00000419881.1	C9JYJ0
RAD51B	ENST00000487270.5 link	c.1037-30550C>A	intron_variant	Intron 10 of 10	1	ENSP00000419471.1	O15315-3
RAD51B	ENST00000488612.5 link	c.1037-86846C>A	intron_variant	Intron 10 of 11	1	ENSP00000420061.1	O15315-4

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6667

AN:

152210

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0702

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0363

Gnomad ASJ

AF:

0.0591

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0387

GnomAD4 exome

AF:

0.0317

AC:

26314

AN:

829804

Hom.:

468

Cov.:

AF XY:

0.0317

AC XY:

12169

AN XY:

383322

show subpopulations

African (AFR)

AF:

0.0669

AC:

1050

AN:

15706

American (AMR)

AF:

0.0286

AC:

AN:

980

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

287

AN:

5134

East Asian (EAS)

AF:

0.00

AC:

AN:

3614

South Asian (SAS)

AF:

0.0250

AC:

410

AN:

16380

European-Finnish (FIN)

AF:

0.0145

AC:

AN:

276

Middle Eastern (MID)

AF:

0.0451

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.0311

AC:

23564

AN:

758904

Other (OTH)

AF:

0.0330

AC:

898

AN:

27190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

1272

2544

3817

5089

6361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1246

2492

3738

4984

6230

<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:

0.0438

AC:

6677

AN:

152328

Hom.:

180

Cov.:

AF XY:

0.0431

AC XY:

3213

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0702

AC:

2918

AN:

41554

American (AMR)

AF:

0.0362

AC:

554

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0591

AC:

205

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.0259

AC:

125

AN:

4828

European-Finnish (FIN)

AF:

0.0258

AC:

274

AN:

10616

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0364

AC:

2477

AN:

68042

Other (OTH)

AF:

0.0383

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

321

641

962

1282

1603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0207

Hom.:

Bravo

AF:

0.0455

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.18

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over