chr17-58692618-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000482007.5(RAD51C):n.-26C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,612,988 control chromosomes in the GnomAD database, including 34,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2768 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31842 hom. )

Consequence

RAD51C
ENST00000482007.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.24

Publications

28 publications found

Variant links:

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

RAD51C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 17-58692618-C-T is Benign according to our data. Variant chr17-58692618-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 324173.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51C	NM_058216.3 link	c.-26C>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000337432.9	NP_478123.1	O43502-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9 link	c.-26C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_058216.3	ENSP00000336701.4		O43502-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28080

AN:

152098

Hom.:

2765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.180

AC:

44995

AN:

250272

AF XY:

0.179

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.204

AC:

298243

AN:

1460772

Hom.:

31842

Cov.:

AF XY:

0.202

AC XY:

146701

AN XY:

726612

show subpopulations

African (AFR)

AF:

0.132

AC:

4406

AN:

33458

American (AMR)

AF:

0.138

AC:

6155

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0890

AC:

2325

AN:

26132

East Asian (EAS)

AF:

0.208

AC:

8254

AN:

39696

South Asian (SAS)

AF:

0.139

AC:

11971

AN:

86154

European-Finnish (FIN)

AF:

0.261

AC:

13871

AN:

53140

Middle Eastern (MID)

AF:

0.113

AC:

599

AN:

5312

European-Non Finnish (NFE)

AF:

0.216

AC:

239838

AN:

1111838

Other (OTH)

AF:

0.179

AC:

10824

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12880

25761

38641

51522

64402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8220

16440

24660

32880

41100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.185

AC:

28097

AN:

152216

Hom.:

2768

Cov.:

AF XY:

0.187

AC XY:

13935

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.137

AC:

5679

AN:

41564

American (AMR)

AF:

0.176

AC:

2699

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0824

AC:

286

AN:

3472

East Asian (EAS)

AF:

0.177

AC:

915

AN:

5168

South Asian (SAS)

AF:

0.139

AC:

671

AN:

4828

European-Finnish (FIN)

AF:

0.264

AC:

2791

AN:

10572

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.212

AC:

14386

AN:

67994

Other (OTH)

AF:

0.167

AC:

352

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1192

2384

3575

4767

5959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.187

Hom.:

754

Bravo

AF:

0.170

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 02, 2014

Leiden Open Variation Database

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Christine Rappaport. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

RAD51C-related disorder

Benign:1

Sep 09, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Breast and Ovarian Cancer Susceptibility

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.74

(source)

DANN

Benign

0.88

PhyloP100

-3.2

PromoterAI

0.33

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over