rs16943176

Variant names:

• chr17-58692526-G-A
• rs16943176
• NM_058216.3:c.-118G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.864
• Publications: 29 publications found

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 Gene-Disease associations (from GenCC):

• RAD51C-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• breast-ovarian cancer, familial, susceptibility to, 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Fanconi anemia complementation group O

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• hereditary breast ovarian cancer syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058216.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51C	NM_058216.3	MANE Select	c.-118G>A		upstream_gene	N/A	NP_478123.1	O43502-1
	RAD51C	NM_002876.4		c.-118G>A		upstream_gene	N/A	NP_002867.1	O43502-2
	RAD51C	NR_103872.2		n.-76G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51C	ENST00000337432.9	TSL:1 MANE Select	c.-118G>A		upstream_gene	N/A	ENSP00000336701.4	O43502-1
	RAD51C	ENST00000421782.3	TSL:1	c.-118G>A		upstream_gene	N/A	ENSP00000391450.2	O43502-2
	RAD51C	ENST00000482007.5	TSL:1	n.-118G>A		upstream_gene	N/A	ENSP00000433332.1	Q7KZJ0

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

African (AFR) AF: 0.129 AC: 3361 AN: 25954

American (AMR) AF: 0.144 AC: 3995 AN: 27746

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 1869 AN: 21686

East Asian (EAS) AF: 0.208 AC: 7797 AN: 37486

South Asian (SAS) AF: 0.137 AC: 10136 AN: 73780

European-Finnish (FIN) AF: 0.257 AC: 10450 AN: 40724

Middle Eastern (MID) AF: 0.102 AC: 353 AN: 3476

European-Non Finnish (NFE) AF: 0.210 AC: 187311 AN: 893374

Other (OTH) AF: 0.176 AC: 8869 AN: 50432

GnomAD4 genome AF: 0.185 AC: 28109 AN: 152232 Hom.: 2775 Cov.: 32 AF XY: 0.187 AC XY: 13940 AN XY: 74414

African (AFR) AF: 0.137 AC: 5675 AN: 41548

American (AMR) AF: 0.177 AC: 2703 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3472

East Asian (EAS) AF: 0.177 AC: 912 AN: 5158

South Asian (SAS) AF: 0.139 AC: 671 AN: 4824

European-Finnish (FIN) AF: 0.265 AC: 2808 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14386 AN: 67998

Other (OTH) AF: 0.166 AC: 352 AN: 2116

Alfa AF: 0.187 Hom.: 7054

Bravo AF: 0.170

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5
DANN	Benign	0.90
PhyloP100		0.86
PromoterAI		0.12	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16943176; hg19: chr17-56769887;