Menu
GeneBe

rs1799782

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

4
4
7

Clinical Significance

Benign criteria provided, single submitter B:1O:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons MANE UniProt
XRCC1NM_006297.3 linkuse as main transcriptc.580C>T p.Arg194Trp missense_variant 6/17 ENST00000262887.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XRCC1ENST00000262887.10 linkuse as main transcriptc.580C>T p.Arg194Trp missense_variant 6/171 NM_006297.3 P1
ENST00000597119.1 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0733
AC:
11141
AN:
152008
Hom.:
622
Cov.:
31
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
GnomAD3 exomes
AF:
0.0946
AC:
23794
AN:
251438
Hom.:
1703
AF XY:
0.0905
AC XY:
12298
AN XY:
135900
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 SAS exome
AF:
0.0935
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.:
33
AF XY:
0.0715
AC XY:
51968
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0639
Gnomad4 AMR exome
AF:
0.146
Gnomad4 ASJ exome
AF:
0.0657
Gnomad4 EAS exome
AF:
0.304
Gnomad4 SAS exome
AF:
0.0923
Gnomad4 FIN exome
AF:
0.0370
Gnomad4 NFE exome
AF:
0.0597
Gnomad4 OTH exome
AF:
0.0803
GnomAD4 genome
AF:
0.0732
AC:
11143
AN:
152126
Hom.:
622
Cov.:
31
AF XY:
0.0739
AC XY:
5495
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0622
Gnomad4 AMR
AF:
0.101
Gnomad4 ASJ
AF:
0.0591
Gnomad4 EAS
AF:
0.292
Gnomad4 SAS
AF:
0.103
Gnomad4 FIN
AF:
0.0370
Gnomad4 NFE
AF:
0.0616
Gnomad4 OTH
AF:
0.0852
Alfa
AF:
0.0682
Hom.:
958
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:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 02, 2020This 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) -
Non-small cell lung carcinoma Other:1
not provided, no classification providedliterature onlyDatabase of Curated Mutations (DoCM)Mar 10, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.36
Cadd
Uncertain
24
Dann
Pathogenic
1.0
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.79
D
MetaRNN
Benign
0.0016
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
0.000030
P;P
PrimateAI
Uncertain
0.65
T
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
T
GERP RS
1.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.68

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.

Other links and lift over

dbSNP: rs1799782; hg19: chr19-44057574; COSMIC: COSV53447553; COSMIC: COSV53447553; API