14-67825181-C-T

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.85-283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 150,654 control chromosomes in the GnomAD database, including 8,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8235 hom., cov: 29)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163

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=-0.94).
• BP6: Variant 14-67825181-C-T is Benign according to our data. Variant chr14-67825181-C-T is described in ClinVar as [Benign]. Clinvar id is 1238204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.85-283C>T		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.85-283C>T		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 48922 AN: 150562 Hom.: 8213 Cov.: 29

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.325 AC: 48976 AN: 150654 Hom.: 8235 Cov.: 29 AF XY: 0.318 AC XY: 23315 AN XY: 73418

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.0837

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.329

Alfa AF: 0.325 Hom.: 980

Bravo AF: 0.324

Asia WGS AF: 0.180 AC: 627 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.8
Dann	Benign	0.56

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: rs8011393; hg19: chr14-68291898;