chr14-67825190-G-A

Position:

• chr14-67825190-G-A

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.85-274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 150,350 control chromosomes in the GnomAD database, including 12,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (12155 hom., cov: 30)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.417

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=-0.93).
• BP6: Variant 14-67825190-G-A is Benign according to our data. Variant chr14-67825190-G-A is described in ClinVar as [Benign]. Clinvar id is 1270763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.85-274G>A		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.85-274G>A		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58177 AN: 150240 Hom.: 12123 Cov.: 30

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.387 AC: 58250 AN: 150350 Hom.: 12155 Cov.: 30 AF XY: 0.379 AC XY: 27730 AN XY: 73206

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.383

Alfa AF: 0.354 Hom.: 5417

Bravo AF: 0.393

Asia WGS AF: 0.227 AC: 792 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.58

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: rs8011690; hg19: chr14-68291907;