Variant chr17-58720846-T-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_058216.3(RAD51C):c.904+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,537,120 control chromosomes in the GnomAD database, including 80,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7206 hom., cov: 32)

Exomes 𝑓: 0.32 ( 73410 hom. )

Consequence

RAD51C
NM_058216.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.289

Variant links:

Genes affected

RAD51C (HGNC:9820): (RAD51 paralog C) This gene is a member of the RAD51 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 other RAD51 paralogs and is reported to be important for Holliday junction resolution. Mutations in this gene are associated with Fanconi anemia-like syndrome. This gene is one of four localized to a region of chromosome 17q23 where amplification occurs frequently in breast tumors. Overexpression of the four genes during amplification has been observed and suggests a possible role in tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RAD51C links:

RAD51C (HGNC:):

RAD51C 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=-0.86).

BP6

Variant 17-58720846-T-C is Benign according to our data. Variant chr17-58720846-T-C is described in ClinVar as [Benign]. Clinvar id is 1275824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58720846-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51C	NM_058216.3 linkuse as main transcript	c.904+34T>C		intron_variant		ENST00000337432.9	NP_478123.1	O43502-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9 linkuse as main transcript	c.904+34T>C		intron_variant		1	NM_058216.3	ENSP00000336701.4		O43502-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45201

AN:

152026

Hom.:

7194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.274

AC:

67295

AN:

245624

Hom.:

10711

AF XY:

0.278

AC XY:

37059

AN XY:

133214

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.000822

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.317

AC:

439023

AN:

1384976

Hom.:

73410

Cov.:

AF XY:

0.316

AC XY:

218797

AN XY:

693348

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.430

Gnomad4 EAS exome

AF:

0.000612

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.297

AC:

45240

AN:

152144

Hom.:

7206

Cov.:

AF XY:

0.291

AC XY:

21637

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.439

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.345

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.334

Hom.:

1680

Bravo

AF:

0.295

Asia WGS

AF:

0.0940

AC:

331

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fanconi anemia complementation group O

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.4

DANN

Benign

0.47

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