rs8015998

Positions:

• chr14-68728314-T-C

Variant summary

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

The XR_007064227.1(LOC105370547):​n.116+176T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,196 control chromosomes in the GnomAD database, including 1,893 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 0.15 (1893 hom., cov: 33)
• Consequence: LOC105370547 XR_007064227.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

LOC105370547 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105370547	XR_007064227.1	n.116+176T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.*12-1494T>C		intron_variant		1		ENSP00000420061

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22958 AN: 152076 Hom.: 1896 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.0724

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.151 AC: 22966 AN: 152196 Hom.: 1893 Cov.: 33 AF XY: 0.156 AC XY: 11583 AN XY: 74412

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0861

Gnomad4 ASJ AF: 0.0724

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.122

Alfa AF: 0.144 Hom.: 332

Bravo AF: 0.134

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8015998; hg19: chr14-69195031;