chr14-68728314-T-C

Variant names:

• chr14-68728314-T-C
• rs8015998
• ENST00000488612.5:c.*12-1494T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000488612.5(RAD51B):​c.*12-1494T>C variant causes a intron 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: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 publications found

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]

RAD51B Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LOC105370547 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC105370547	XR_007064227.1	n.116+176T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.*12-1494T>C		intron_variant	Intron 11 of 11	1		ENSP00000420061.1

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

African (AFR) AF: 0.162 AC: 6746 AN: 41524

American (AMR) AF: 0.0861 AC: 1317 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0724 AC: 251 AN: 3468

East Asian (EAS) AF: 0.184 AC: 954 AN: 5184

South Asian (SAS) AF: 0.143 AC: 692 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2984 AN: 10586

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9686 AN: 68000

Other (OTH) AF: 0.122 AC: 257 AN: 2112

Alfa AF: 0.145 Hom.: 351

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
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8015998; hg19: chr14-69195031;