rs17222691

Positions:

• chr17-58693735-C-T

Variant summary

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

The NM_058216.3(RAD51C):​c.145+947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,948 control chromosomes in the GnomAD database, including 2,495 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 0.17 (2495 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RAD51C NM_058216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51C	NM_058216.3	c.145+947C>T		intron_variant		ENST00000337432.9	NP_478123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9	c.145+947C>T		intron_variant		1	NM_058216.3	ENSP00000336701.4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25663 AN: 151830 Hom.: 2493 Cov.: 32

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.156

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.169 AC: 25679 AN: 151948 Hom.: 2495 Cov.: 32 AF XY: 0.172 AC XY: 12744 AN XY: 74234

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.154

Alfa AF: 0.187 Hom.: 2971

Bravo AF: 0.153

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17222691; hg19: chr17-56771096; COSMIC: COSV53622241; COSMIC: COSV53622241;