rs16943176

Positions:

• chr17-58692526-G-A
• chr17-58692526-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The 17-58692526-G-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 ENST00000583539.5 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.864

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]

ACMG classification

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/exons	MANE	Protein	UniProt
RAD51C	XM_006722004.4			upstream_gene_variant			XP_006722067.1
RAD51C	NR_103873.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000461271.6			upstream_gene_variant		5		ENSP00000464056
RAD51C	ENST00000583539.5			upstream_gene_variant		2		ENSP00000463121	A2
RAD51C	ENST00000487921.5			upstream_gene_variant		3
RAD51C	ENST00000697675.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28092 AN: 152118 Hom.: 2772 Cov.: 32

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.: 16 AF XY: 0.197 AC XY: 116938 AN XY: 593162

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.: 32 AF XY: 0.187 AC XY: 13940 AN XY: 74414

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Other links and lift over

dbSNP: rs16943176; hg19: chr17-56769887;