rs8016149

Variant names:

• chr14-68566272-T-G
• rs8016149
• ENST00000487861.5:c.1037-44734T>G

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-44734T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,104 control chromosomes in the GnomAD database, including 6,148 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 0.27 (6148 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553
• Publications: 5 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-44734T>G		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1037-28213T>G		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321809.2	c.1037-36391T>G		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.1037-44734T>G		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-28213T>G		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-84509T>G		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40753 AN: 151986 Hom.: 6144 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.268 AC: 40769 AN: 152104 Hom.: 6148 Cov.: 32 AF XY: 0.265 AC XY: 19722 AN XY: 74358

African (AFR) AF: 0.395 AC: 16350 AN: 41440

American (AMR) AF: 0.250 AC: 3825 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1990 AN: 5170

South Asian (SAS) AF: 0.279 AC: 1347 AN: 4828

European-Finnish (FIN) AF: 0.158 AC: 1671 AN: 10600

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13610 AN: 67998

Other (OTH) AF: 0.298 AC: 626 AN: 2104

Alfa AF: 0.231 Hom.: 5385

Bravo AF: 0.283

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		0.55
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: rs8016149; hg19: chr14-69032989;