14-67835047-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133510.4(RAD51B):c.199-33G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,498,014 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (86 hom., cov: 32)
  • Exomes 𝑓: 0.015 (259 hom.)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0130

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-67835047-G-T is Benign according to our data. Variant chr14-67835047-G-T is described in ClinVar as [Benign]. Clinvar id is 1248492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.199-33G>T		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.199-33G>T		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 3946 AN: 130992 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00312

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.00809

Gnomad MID AF: 0.0238

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0191 AC: 4185 AN: 219212 Hom.: 68 AF XY: 0.0177 AC XY: 2099 AN XY: 118620

Gnomad AFR exome AF: 0.0801

Gnomad AMR exome AF: 0.00577

Gnomad ASJ exome AF: 0.00191

Gnomad EAS exome AF: 0.0524

Gnomad SAS exome AF: 0.0164

Gnomad FIN exome AF: 0.00603

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0140

GnomAD4 exome AF: 0.0146 AC: 20011 AN: 1366912 Hom.: 259 Cov.: 21 AF XY: 0.0145 AC XY: 9907 AN XY: 684996

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.00533

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0608

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.00716

Gnomad4 NFE exome AF: 0.0124

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0303 AC: 3975 AN: 131102 Hom.: 86 Cov.: 32 AF XY: 0.0297 AC XY: 1907 AN XY: 64290

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00312

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.0175

Gnomad4 FIN AF: 0.00809

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0264

Alfa AF: 0.0163 Hom.: 9

Bravo AF: 0.0285

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Hereditary breast ovarian cancer syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.2
Dann	Benign	0.53

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: rs184815928; hg19: chr14-68301764; COSMIC: COSV104699675;