rs8016149

chr14-68566272-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.64).
• 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/exons	MANE	UniProt
RAD51B	NM_001321809.2	c.1037-36391T>G		intron_variant
RAD51B	NM_001321810.2	c.1037-36391T>G		intron_variant
RAD51B	NM_001321815.1	c.923-44886T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000487270.5	c.1037-28213T>G		intron_variant		1
RAD51B	ENST00000487861.5	c.1037-44734T>G		intron_variant		1
RAD51B	ENST00000488612.5	c.1037-84509T>G		intron_variant		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

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.298

Alfa AF: 0.221 Hom.: 3690

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8016149; hg19: chr14-69032989;