17-58724780-C-T

Variant names:

• chr17-58724780-C-T
• rs304270
• NM_058216.3:c.965+680C>T

Variant summary

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

The NM_058216.3(RAD51C):​c.965+680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,972 control chromosomes in the GnomAD database, including 31,050 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 0.64 (31050 hom., cov: 32)
• Consequence: RAD51C NM_058216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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]

LOC105371843 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51C	NM_058216.3	c.965+680C>T		intron_variant	Intron 7 of 8	ENST00000337432.9	NP_478123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9	c.965+680C>T		intron_variant	Intron 7 of 8	1	NM_058216.3	ENSP00000336701.4

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96455 AN: 151854 Hom.: 31001 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.635 AC: 96553 AN: 151972 Hom.: 31050 Cov.: 32 AF XY: 0.634 AC XY: 47112 AN XY: 74296

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.632

Alfa AF: 0.617 Hom.: 15314

Bravo AF: 0.621

Asia WGS AF: 0.548 AC: 1901 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.55

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: rs304270; hg19: chr17-56802141;