chr14-68497029-C-T

Variant names:

• chr14-68497029-C-T
• rs765899
• ENST00000487861.5:c.1036+28779C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000487861.5(RAD51B):​c.1036+28779C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,199,680 control chromosomes in the GnomAD database, including 94,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9737 hom., cov: 32)
  • Exomes 𝑓: 0.40 (85134 hom.)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.694
• Publications: 14 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-68497029-C-T is Benign according to our data. Variant chr14-68497029-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1036+28779C>T		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1036+28779C>T		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321812.1	c.1036+28779C>T		intron_variant	Intron 9 of 9		NP_001308741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1036+28779C>T		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+28779C>T		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+28779C>T		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50614 AN: 152018 Hom.: 9728 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.396 AC: 414788 AN: 1047544 Hom.: 85134 AF XY: 0.402 AC XY: 207264 AN XY: 515038

African (AFR) AF: 0.122 AC: 2646 AN: 21710

American (AMR) AF: 0.541 AC: 12591 AN: 23262

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 6403 AN: 15962

East Asian (EAS) AF: 0.375 AC: 6554 AN: 17470

South Asian (SAS) AF: 0.563 AC: 38692 AN: 68766

European-Finnish (FIN) AF: 0.362 AC: 8273 AN: 22858

Middle Eastern (MID) AF: 0.391 AC: 1650 AN: 4222

European-Non Finnish (NFE) AF: 0.387 AC: 322705 AN: 834004

Other (OTH) AF: 0.389 AC: 15274 AN: 39290

GnomAD4 genome AF: 0.333 AC: 50631 AN: 152136 Hom.: 9737 Cov.: 32 AF XY: 0.338 AC XY: 25116 AN XY: 74354

African (AFR) AF: 0.135 AC: 5602 AN: 41522

American (AMR) AF: 0.458 AC: 7005 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1407 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2067 AN: 5178

South Asian (SAS) AF: 0.571 AC: 2753 AN: 4822

European-Finnish (FIN) AF: 0.368 AC: 3885 AN: 10548

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26806 AN: 67974

Other (OTH) AF: 0.343 AC: 724 AN: 2112

Alfa AF: 0.379 Hom.: 35555

Bravo AF: 0.326

Asia WGS AF: 0.480 AC: 1671 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2019

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	-0.86
CADD	Benign	0.45
DANN	Benign	0.24
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs765899; hg19: chr14-68963746; COSMIC: COSV66845116;