dbSNP rs16943176: RAD51C:c.-118G>A (chr17-58692526-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_058216.3(RAD51C):c.-118G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,326,890 control chromosomes in the GnomAD database, including 27,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2775 hom., cov: 32)

Exomes 𝑓: 0.20 ( 24397 hom. )

Consequence

RAD51C
NM_058216.3 upstream_gene

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.864

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-58692526-G-A is Benign according to our data. Variant chr17-58692526-G-A is described in ClinVar as [Benign]. Clinvar id is 1250767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51C	NM_058216.3 link	c.-118G>A		upstream_gene_variant		ENST00000337432.9	NP_478123.1	O43502-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9 link	c.-118G>A		upstream_gene_variant		1	NM_058216.3	ENSP00000336701.4		O43502-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28092

AN:

152118

Hom.:

2772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.199

AC:

234141

AN:

1174658

Hom.:

24397

Cov.:

AF XY:

0.197

AC XY:

116938

AN XY:

593162

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.0862

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.185

AC:

28109

AN:

152232

Hom.:

2775

Cov.:

AF XY:

0.187

AC XY:

13940

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.0824

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.265

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.191

Hom.:

4698

Bravo

AF:

0.170

Asia WGS

AF:

0.164

AC:

570

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.5

DANN

Benign

0.90

Splicing

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