rs45511291

Variant names:

• chr17-58694980-A-G
• rs45511291
• NM_058216.3:c.195A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-58694980-A-G
• chr17-58694980-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_058216.3(RAD51C):​c.195A>G​(p.Arg65Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000915 in 1,614,146 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R65R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0014 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (23 hom.)
• Consequence: RAD51C NM_058216.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:22
• Conservation: PhyloP100: 3.64
• Publications: 5 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=-0.53).
• BP6: Variant 17-58694980-A-G is Benign according to our data. Variant chr17-58694980-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00141 (215/152318) while in subpopulation EAS AF = 0.036 (187/5190). AF 95% confidence interval is 0.0318. There are 7 homozygotes in GnomAd4. There are 107 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR,AD gene

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.195A>G	p.Arg65Arg	synonymous	Exon 2 of 9	NP_478123.1	O43502-1
	RAD51C	NM_002876.4		c.195A>G	p.Arg65Arg	synonymous	Exon 2 of 2	NP_002867.1	O43502-2
	RAD51C	NR_103872.2		n.237A>G		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51C	ENST00000337432.9	TSL:1 MANE Select	c.195A>G	p.Arg65Arg	synonymous	Exon 2 of 9	ENSP00000336701.4	O43502-1
	RAD51C	ENST00000421782.3	TSL:1	c.195A>G	p.Arg65Arg	synonymous	Exon 2 of 2	ENSP00000391450.2	O43502-2
	RAD51C	ENST00000482007.5	TSL:1	n.195A>G		non_coding_transcript_exon	Exon 2 of 8	ENSP00000433332.1	Q7KZJ0

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152200 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00303 AC: 762 AN: 251446 AF XY: 0.00267

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0405

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000863 AC: 1262 AN: 1461828 Hom.: 23 Cov.: 31 AF XY: 0.000799 AC XY: 581 AN XY: 727218

African (AFR) AF: 0.000358 AC: 12 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0294 AC: 1167 AN: 39688

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111968

Other (OTH) AF: 0.000729 AC: 44 AN: 60392

GnomAD4 genome AF: 0.00141 AC: 215 AN: 152318 Hom.: 7 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74476

African (AFR) AF: 0.000481 AC: 20 AN: 41572

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0360 AC: 187 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000782 Hom.: 6

Bravo AF: 0.00176

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	3	Breast-ovarian cancer, familial, susceptibility to, 3 (3)
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	3	not provided (3)
-	-	2	Fanconi anemia complementation group O (2)
-	-	1	Breast and Ovarian Cancer Susceptibility (1)
-	-	1	Breast and/or ovarian cancer (1)
-	-	1	Fanconi anemia (1)
-	-	1	Malignant tumor of breast (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		3.6
PromoterAI		0.010	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs45511291; hg19: chr17-56772341;