Variant chr14-67823655-T-G 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.84+28T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,559,548 control chromosomes in the GnomAD database, including 91,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8319 hom., cov: 32)

Exomes 𝑓: 0.34 ( 82826 hom. )

Consequence

RAD51B
NM_133510.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.182

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:

RAD51B (HGNC:):

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=-0.88).

BP6

Variant 14-67823655-T-G is Benign according to our data. Variant chr14-67823655-T-G is described in ClinVar as [Benign]. Clinvar id is 1264893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
RAD51B	NM_133510.4 linkuse as main transcript	c.84+28T>G		intron_variant		ENST00000471583.6	NP_598194.1	O15315-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6 linkuse as main transcript	c.84+28T>G		intron_variant		1	NM_133510.4	ENSP00000418859.1		O15315-2

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49168

AN:

151950

Hom.:

8298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.0744

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.330

GnomAD3 exomes

AF:

0.293

AC:

71103

AN:

242970

Hom.:

11482

AF XY:

0.295

AC XY:

38727

AN XY:

131276

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.0743

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.337

AC:

473847

AN:

1407480

Hom.:

82826

Cov.:

AF XY:

0.334

AC XY:

234644

AN XY:

702678

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.0850

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.360

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.324

AC:

49222

AN:

152068

Hom.:

8319

Cov.:

AF XY:

0.316

AC XY:

23460

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.0748

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.337

Hom.:

2098

Bravo

AF:

0.323

Asia WGS

AF:

0.179

AC:

623

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.88

CADD

Benign

4.7

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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