rs17222691

Variant names:

• chr17-58693735-C-T
• rs17222691
• NM_058216.3:c.145+947C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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):

• breast-ovarian cancer, familial, susceptibility to, 3

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

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51C	NM_058216.3	MANE Select	c.145+947C>T		intron	N/A	NP_478123.1
	RAD51C	NM_002876.4		c.145+947C>T		intron	N/A	NP_002867.1
	RAD51C	NR_103872.2		n.187+947C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51C	ENST00000337432.9	TSL:1 MANE Select	c.145+947C>T		intron	N/A	ENSP00000336701.4
	RAD51C	ENST00000421782.3	TSL:1	c.145+947C>T		intron	N/A	ENSP00000391450.2
	RAD51C	ENST00000482007.5	TSL:1	n.145+947C>T		intron	N/A	ENSP00000433332.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0827 AC: 3428 AN: 41456

American (AMR) AF: 0.170 AC: 2588 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.178 AC: 922 AN: 5178

South Asian (SAS) AF: 0.140 AC: 673 AN: 4814

European-Finnish (FIN) AF: 0.264 AC: 2781 AN: 10528

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14363 AN: 67954

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.182 Hom.: 3652

Bravo AF: 0.153

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.71
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17222691; hg19: chr17-56771096; COSMIC: COSV53622241;