17-58720846-T-C

Variant names:

Variant summary

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

The NM_058216.3(RAD51C):c.904+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,537,120 control chromosomes in the GnomAD database, including 80,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7206 hom., cov: 32)

Exomes 𝑓: 0.32 ( 73410 hom. )

Consequence

RAD51C
NM_058216.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.289

Publications

15 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=-0.86).

BP6

Variant 17-58720846-T-C is Benign according to our data. Variant chr17-58720846-T-C is described in ClinVar as Benign. ClinVar VariationId is 1275824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51C	NM_058216.3 link	c.904+34T>C		intron_variant	Intron 6 of 8	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.904+34T>C		intron_variant	Intron 6 of 8	1	NM_058216.3	ENSP00000336701.4		O43502-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45201

AN:

152026

Hom.:

7194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.336

GnomAD2 exomes

AF:

0.274

AC:

67295

AN:

245624

AF XY:

0.278

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.000822

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.317

AC:

439023

AN:

1384976

Hom.:

73410

Cov.:

AF XY:

0.316

AC XY:

218797

AN XY:

693348

show subpopulations

African (AFR)

AF:

0.274

AC:

8728

AN:

31890

American (AMR)

AF:

0.197

AC:

8760

AN:

44440

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

11015

AN:

25630

East Asian (EAS)

AF:

0.000612

AC:

AN:

39218

South Asian (SAS)

AF:

0.199

AC:

16856

AN:

84542

European-Finnish (FIN)

AF:

0.301

AC:

14982

AN:

49764

Middle Eastern (MID)

AF:

0.429

AC:

1870

AN:

4364

European-Non Finnish (NFE)

AF:

0.342

AC:

358296

AN:

1047390

Other (OTH)

AF:

0.320

AC:

18492

AN:

57738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14471

28942

43414

57885

72356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10966

21932

32898

43864

54830

<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:

0.297

AC:

45240

AN:

152144

Hom.:

7206

Cov.:

AF XY:

0.291

AC XY:

21637

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.271

AC:

11257

AN:

41518

American (AMR)

AF:

0.261

AC:

3988

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1525

AN:

3470

East Asian (EAS)

AF:

0.00231

AC:

AN:

5190

South Asian (SAS)

AF:

0.179

AC:

866

AN:

4828

European-Finnish (FIN)

AF:

0.292

AC:

3094

AN:

10580

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23445

AN:

67956

Other (OTH)

AF:

0.331

AC:

700

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1620

3240

4861

6481

8101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.332

Hom.:

1707

Bravo

AF:

0.295

Asia WGS

AF:

0.0940

AC:

331

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: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 complementation group O

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: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

-0.86

CADD

Benign

5.4

(source)

DANN

Benign

0.47

PhyloP100

0.29

Mutation Taster

=100/0

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