Variant 14-67835059-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133510.4(RAD51B):c.199-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,488,820 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 119 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 120 hom. )

Consequence

RAD51B
NM_133510.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.322

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-67835059-C-T is Benign according to our data. Variant chr14-67835059-C-T is described in ClinVar as [Benign]. Clinvar id is 1231988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4 linkuse as main transcript	c.199-21C>T		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6 linkuse as main transcript	c.199-21C>T		intron_variant		1	NM_133510.4	P4	O15315-2

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3631

AN:

149092

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00904

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00357

Gnomad FIN

AF:

0.00116

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00367

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.00861

AC:

2095

AN:

243418

Hom.:

AF XY:

0.00761

AC XY:

1002

AN XY:

131712

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.00615

Gnomad ASJ exome

AF:

0.00960

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00253

Gnomad FIN exome

AF:

0.00177

Gnomad NFE exome

AF:

0.00362

Gnomad OTH exome

AF:

0.00809

GnomAD4 exome

AF:

0.00559

AC:

7489

AN:

1339622

Hom.:

120

Cov.:

AF XY:

0.00543

AC XY:

3645

AN XY:

671732

show subpopulations

Gnomad4 AFR exome

AF:

0.0818

Gnomad4 AMR exome

AF:

0.00660

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00350

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00936

GnomAD4 genome

AF:

0.0244

AC:

3635

AN:

149198

Hom.:

119

Cov.:

AF XY:

0.0231

AC XY:

1685

AN XY:

72792

show subpopulations

Gnomad4 AFR

AF:

0.0773

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00904

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00357

Gnomad4 FIN

AF:

0.00116

Gnomad4 NFE

AF:

0.00367

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00966

Hom.:

Bravo

AF:

0.0270

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 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

-0.82

CADD

Benign

6.2

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over