14-68588811-T-C

Variant names:

• chr14-68588811-T-C
• rs2256608
• ENST00000487861.5:c.1037-22195T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000487861.5(RAD51B):​c.1037-22195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,138 control chromosomes in the GnomAD database, including 50,605 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 0.81 (50605 hom., cov: 31)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-22195T>C		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1037-5674T>C		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321809.2	c.1037-13852T>C		intron_variant	Intron 10 of 11		NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-22195T>C		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-5674T>C		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-61970T>C		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123692 AN: 152018 Hom.: 50557 Cov.: 31

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.793

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.814 AC: 123797 AN: 152138 Hom.: 50605 Cov.: 31 AF XY: 0.816 AC XY: 60677 AN XY: 74386

African (AFR) AF: 0.860 AC: 35714 AN: 41520

American (AMR) AF: 0.775 AC: 11843 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3470

East Asian (EAS) AF: 0.699 AC: 3618 AN: 5178

South Asian (SAS) AF: 0.757 AC: 3642 AN: 4812

European-Finnish (FIN) AF: 0.879 AC: 9308 AN: 10590

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54510 AN: 67980

Other (OTH) AF: 0.795 AC: 1675 AN: 2108

Alfa AF: 0.797 Hom.: 51817

Bravo AF: 0.807

Asia WGS AF: 0.731 AC: 2541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.1
DANN	Benign	0.41
PhyloP100		-0.27
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: rs2256608; hg19: chr14-69055528;