rs1799782

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_006297.3(XRCC1):c.580C>T(p.Arg194Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 1,613,942 control chromosomes in the GnomAD database, including 5,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 622 hom., cov: 31)

Exomes 𝑓: 0.071 ( 5357 hom. )

Consequence

XRCC1
NM_006297.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

XRCC1 links:

ENSG00000269177 (HGNC:):

ENSG00000269177 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 (MetaRNN=0.0016328394).

BP6

Variant 19-43553422-G-A is Benign according to our data. Variant chr19-43553422-G-A is described in ClinVar as [Benign]. Clinvar id is 376355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3 link	c.580C>T	p.Arg194Trp	missense_variant	Exon 6 of 17	ENST00000262887.10	NP_006288.2	P18887B2RCY5Q59HH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10 link	c.580C>T	p.Arg194Trp	missense_variant	Exon 6 of 17	1	NM_006297.3	ENSP00000262887.5		P18887

Frequencies

GnomAD3 genomes

AF:

0.0733

AC:

11141

AN:

152008

Hom.:

622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0622

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0591

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0616

Gnomad OTH

AF:

0.0852

GnomAD2 exomes

AF:

0.0946

AC:

23794

AN:

251438

AF XY:

0.0905

show subpopulations

Gnomad AFR exome

AF:

0.0599

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.0686

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.0361

Gnomad NFE exome

AF:

0.0621

Gnomad OTH exome

AF:

0.0831

GnomAD4 exome

AF:

0.0712

AC:

104065

AN:

1461816

Hom.:

5357

Cov.:

AF XY:

0.0715

AC XY:

51968

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0639

AC:

2140

AN:

33478

Gnomad4 AMR exome

AF:

0.146

AC:

6514

AN:

44720

Gnomad4 ASJ exome

AF:

0.0657

AC:

1718

AN:

26136

Gnomad4 EAS exome

AF:

0.304

AC:

12072

AN:

39696

Gnomad4 SAS exome

AF:

0.0923

AC:

7965

AN:

86256

Gnomad4 FIN exome

AF:

0.0370

AC:

1975

AN:

53414

Gnomad4 NFE exome

AF:

0.0597

AC:

66380

AN:

1111956

Gnomad4 Remaining exome

AF:

0.0803

AC:

4847

AN:

60396

Heterozygous variant carriers

5448

10897

16345

21794

27242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

2682

5364

8046

10728

13410

<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:

0.0732

AC:

11143

AN:

152126

Hom.:

622

Cov.:

AF XY:

0.0739

AC XY:

5495

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0622

AC:

0.0621687

AN:

0.0621687

Gnomad4 AMR

AF:

0.101

AC:

0.101321

AN:

0.101321

Gnomad4 ASJ

AF:

0.0591

AC:

0.0591119

AN:

0.0591119

Gnomad4 EAS

AF:

0.292

AC:

0.292394

AN:

0.292394

Gnomad4 SAS

AF:

0.103

AC:

0.102911

AN:

0.102911

Gnomad4 FIN

AF:

0.0370

AC:

0.0370475

AN:

0.0370475

Gnomad4 NFE

AF:

0.0616

AC:

0.0615769

AN:

0.0615769

Gnomad4 OTH

AF:

0.0852

AC:

0.0852273

AN:

0.0852273

Heterozygous variant carriers

508

1015

1523

2030

2538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0703

Hom.:

2201

Bravo

AF:

0.0800

TwinsUK

AF:

0.0604

AC:

224

ALSPAC

AF:

0.0579

AC:

223

ESP6500AA

AF:

0.0561

AC:

247

ESP6500EA

AF:

0.0645

AC:

555

ExAC

AF:

0.0928

AC:

11262

Asia WGS

AF:

0.189

AC:

657

AN:

3478

EpiCase

AF:

0.0694

EpiControl

AF:

0.0674

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 02, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17630853, 26434847, 25227852, 25340946, 24497981, 25169084, 24039945, 23990873, 23320983, 22639094, 29484706, 19124519, 16324877, 20385586, 19465687, 20431719, 22983827, 21499756, 20553853, 21987112, 12893086, 20218899, 20331623, 20863780, 20332227, 20052722, 19481337, 15113441) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.086

.;T;.;.

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.84

.;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-4.4

D;D;.;.

REVEL

Benign

0.20

Sift

Uncertain

0.0010

D;D;.;.

Sift4G

Pathogenic

0.0010

D;D;D;.

Polyphen

0.91

.;P;.;.

Vest4

0.32

MPC

0.56

ClinPred

0.041

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.68

Mutation Taster

=81/19

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over