Variant 15-40695330-G-C 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_002875.5(RAD51):c.-98G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,656 control chromosomes in the GnomAD database, including 1,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1476 hom., cov: 33)

Exomes 𝑓: 0.067 ( 2 hom. )

Consequence

RAD51
NM_002875.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.280

Variant links:

Genes affected

RAD51 (HGNC:9817): (RAD51 recombinase) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

RAD51 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=-0.81).

BP6

Variant 15-40695330-G-C is Benign according to our data. Variant chr15-40695330-G-C is described in ClinVar as [Benign]. Clinvar id is 13128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51	NM_002875.5 linkuse as main transcript	c.-98G>C		5_prime_UTR_variant	1/10	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8 linkuse as main transcript	c.-98G>C		5_prime_UTR_variant	1/10	1	NM_002875.5	ENSP00000267868	P1	Q06609-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18610

AN:

152148

Hom.:

1456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0928

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0748

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.0667

AC:

AN:

390

Hom.:

Cov.:

AF XY:

0.0686

AC XY:

AN XY:

306

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0566

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.123

AC:

18675

AN:

152266

Hom.:

1476

Cov.:

AF XY:

0.123

AC XY:

9126

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.0750

Gnomad4 ASJ

AF:

0.0441

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.0928

Gnomad4 NFE

AF:

0.0748

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.109

Hom.:

131

Bravo

AF:

0.126

Asia WGS

AF:

0.130

AC:

452

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

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 22, 2018	This variant is associated with the following publications: (PMID: 26117002, 22487057, 24930116, 24604328, 23161237, 11248061, 19606696, 24040396, 21647442, 24859942, 22611952, 16398215, 11535547, 21708019, 20640595, 20623332, 20454923, 20396943, 17999359) -

Breast cancer, susceptibility to, in BRCA1 and BRCA2 carriers

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.1

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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