rs10483813

Positions:

• chr14-68564567-T-A
• chr14-68564567-T-C

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-46439T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,188 control chromosomes in the GnomAD database, including 2,689 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 0.17 (2689 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.63

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]

LOC124903335 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903335	XR_007064225.1	n.102+582A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487270.5	c.1037-29918T>A		intron_variant		1		ENSP00000419471
RAD51B	ENST00000487861.5	c.1037-46439T>A		intron_variant		1		ENSP00000419881
RAD51B	ENST00000488612.5	c.1037-86214T>A		intron_variant		1		ENSP00000420061

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26096 AN: 152070 Hom.: 2689 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.172 AC: 26122 AN: 152188 Hom.: 2689 Cov.: 32 AF XY: 0.170 AC XY: 12670 AN XY: 74410

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.162

Alfa AF: 0.121 Hom.: 237

Bravo AF: 0.164

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0040
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10483813; hg19: chr14-69031284;