rs28363312

Positions:

• chr17-58710932-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337432.9(RAD51C):​c.837+942C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,026 control chromosomes in the GnomAD database, including 2,464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2464 hom., cov: 32)
• Consequence: RAD51C ENST00000337432.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51C	NM_058216.3	c.837+942C>A		intron_variant		ENST00000337432.9	NP_478123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9	c.837+942C>A		intron_variant		1	NM_058216.3	ENSP00000336701	P2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22010 AN: 151908 Hom.: 2458 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.145 AC: 22043 AN: 152026 Hom.: 2464 Cov.: 32 AF XY: 0.148 AC XY: 10989 AN XY: 74308

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.0778

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.126

Alfa AF: 0.109 Hom.: 231

Bravo AF: 0.147

Asia WGS AF: 0.297 AC: 1029 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs28363312; hg19: chr17-56788293;