rs2145157

Positions:

• chr14-68600921-A-G

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-10085A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,010 control chromosomes in the GnomAD database, including 9,492 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 0.35 (9492 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_001321809.2	c.1037-1742A>G		intron_variant
RAD51B	NM_001321810.2	c.1037-1742A>G		intron_variant
RAD51B	NM_001321815.1	c.923-10237A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-10085A>G		intron_variant		1
RAD51B	ENST00000488612.5	c.1037-49860A>G		intron_variant		1
RAD51B	ENST00000478014.5	n.384-82016A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52513 AN: 151892 Hom.: 9488 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.346 AC: 52538 AN: 152010 Hom.: 9492 Cov.: 32 AF XY: 0.344 AC XY: 25544 AN XY: 74304

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.328

Alfa AF: 0.374 Hom.: 22610

Bravo AF: 0.333

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.5
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2145157; hg19: chr14-69067638;