chr14-67832095-G-T

Position:

• chr14-67832095-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133510.4(RAD51B):​c.199-2985G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,276 control chromosomes in the GnomAD database, including 982 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 0.097 (982 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.199-2985G>T		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.199-2985G>T		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14840 AN: 152158 Hom.: 983 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.0974 AC: 14828 AN: 152276 Hom.: 982 Cov.: 32 AF XY: 0.0974 AC XY: 7250 AN XY: 74454

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.00616

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.119

Alfa AF: 0.111 Hom.: 512

Bravo AF: 0.0963

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.96
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs11626809; hg19: chr14-68298812;