14-68193711-T-C

Position:

• chr14-68193711-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133510.4(RAD51B):​c.757-98173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,140 control chromosomes in the GnomAD database, including 49,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.80 (49307 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-68193711-T-C is Benign according to our data. Variant chr14-68193711-T-C is described in ClinVar as [Benign]. Clinvar id is 225821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.757-98173T>C		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.757-98173T>C		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121926 AN: 152022 Hom.: 49292 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.802 AC: 121971 AN: 152140 Hom.: 49307 Cov.: 32 AF XY: 0.806 AC XY: 59945 AN XY: 74394

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.779

Alfa AF: 0.822 Hom.: 14169

Bravo AF: 0.792

Asia WGS AF: 0.865 AC: 3009 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2588809; hg19: chr14-68660428;