ENST00000488612.5:c.*11+9171T>C

Variant names:

• chr14-68660027-T-C
• rs7141529
• ENST00000488612.5:c.*11+9171T>C

Variant summary

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

The ENST00000488612.5(RAD51B):​c.*11+9171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,066 control chromosomes in the GnomAD database, including 21,886 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 0.53 (21886 hom., cov: 32)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 49 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

ENSG00000258623 (HGNC:58171):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488612.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_001321818.2		c.1037-22910T>C		intron	N/A	NP_001308747.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000488612.5	TSL:1	c.*11+9171T>C		intron	N/A	ENSP00000420061.1
	RAD51B	ENST00000478014.5	TSL:3	n.384-22910T>C		intron	N/A
	RAD51B	ENST00000553595.5	TSL:3	n.614-22910T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80976 AN: 151948 Hom.: 21875 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.533 AC: 81029 AN: 152066 Hom.: 21886 Cov.: 32 AF XY: 0.536 AC XY: 39870 AN XY: 74324

African (AFR) AF: 0.544 AC: 22546 AN: 41460

American (AMR) AF: 0.555 AC: 8488 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3470

East Asian (EAS) AF: 0.809 AC: 4194 AN: 5182

South Asian (SAS) AF: 0.583 AC: 2806 AN: 4812

European-Finnish (FIN) AF: 0.493 AC: 5209 AN: 10572

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34229 AN: 67968

Other (OTH) AF: 0.518 AC: 1092 AN: 2110

Alfa AF: 0.516 Hom.: 89530

Bravo AF: 0.541

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		-0.46
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: rs7141529; hg19: chr14-69126744;