ENST00000487270.5:c.*1003G>A

Variant names:

• chr14-68595606-G-A
• rs963917
• ENST00000487270.5:c.*1003G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.321
• Publications: 16 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487270.5. 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_133509.5		c.*1003G>A		3_prime_UTR	Exon 11 of 11	NP_598193.2
	RAD51B	NM_001321821.2		c.1037-15400G>A		intron	N/A	NP_001308750.1
	RAD51B	NM_001321809.2		c.1037-7057G>A		intron	N/A	NP_001308738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487270.5	TSL:1	c.*1003G>A		3_prime_UTR	Exon 11 of 11	ENSP00000419471.1
	RAD51B	ENST00000487861.5	TSL:1	c.1037-15400G>A		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000488612.5	TSL:1	c.1037-55175G>A		intron	N/A	ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40572 AN: 151944 Hom.: 6113 Cov.: 32

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.: 32 AF XY: 0.308 AC XY: 129656 AN XY: 421220

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

GnomAD4 genome AF: 0.267 AC: 40572 AN: 152062 Hom.: 6112 Cov.: 32 AF XY: 0.273 AC XY: 20273 AN XY: 74326

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: 77 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21023 AN: 67982

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.295 Hom.: 16906

Bravo AF: 0.257

Asia WGS AF: 0.411 AC: 1427 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.70
PhyloP100		0.32
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: rs963917; hg19: chr14-69062323; COSMIC: COSV66848203; COSMIC: COSV66848203;