chr14-67864720-G-A

Variant names:

• chr14-67864720-G-A
• rs961700
• NM_133510.4:c.316-283G>A

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0130
• Publications: 7 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=-0.82).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_133510.4	MANE Select	c.316-283G>A		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.316-283G>A		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.316-283G>A		intron	N/A	NP_598193.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.316-283G>A		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.316-283G>A		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.316-283G>A		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61668 AN: 151844 Hom.: 13526 Cov.: 32

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

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

GnomAD4 genome AF: 0.406 AC: 61738 AN: 151962 Hom.: 13552 Cov.: 32 AF XY: 0.397 AC XY: 29539 AN XY: 74316

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.81
PhyloP100		0.013
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs961700; hg19: chr14-68331437; COSMIC: COSV107484910; COSMIC: COSV107484910;