19-43553422-G-A
Position:
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
NM_006297.3 missense
Scores
4
4
7
Clinical Significance
Conservation
PhyloP100: 1.53
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 |
---|---|---|---|---|---|---|---|
XRCC1 | NM_006297.3 | c.580C>T | p.Arg194Trp | missense_variant | 6/17 | ENST00000262887.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC1 | ENST00000262887.10 | c.580C>T | p.Arg194Trp | missense_variant | 6/17 | 1 | NM_006297.3 | P1 | |
ENST00000597119.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0733 AC: 11141AN: 152008Hom.: 622 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
11141
AN:
152008
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0946 AC: 23794AN: 251438Hom.: 1703 AF XY: 0.0905 AC XY: 12298AN XY: 135900
GnomAD3 exomes
AF:
AC:
23794
AN:
251438
Hom.:
AF XY:
AC XY:
12298
AN XY:
135900
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0712 AC: 104065AN: 1461816Hom.: 5357 Cov.: 33 AF XY: 0.0715 AC XY: 51968AN XY: 727210
GnomAD4 exome
AF:
AC:
104065
AN:
1461816
Hom.:
Cov.:
33
AF XY:
AC XY:
51968
AN XY:
727210
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0732 AC: 11143AN: 152126Hom.: 622 Cov.: 31 AF XY: 0.0739 AC XY: 5495AN XY: 74364
GnomAD4 genome
?
AF:
AC:
11143
AN:
152126
Hom.:
Cov.:
31
AF XY:
AC XY:
5495
AN XY:
74364
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
224
ALSPAC
AF:
AC:
223
ESP6500AA
AF:
AC:
247
ESP6500EA
AF:
AC:
555
ExAC
?
AF:
AC:
11262
Asia WGS
AF:
AC:
657
AN:
3478
EpiCase
AF:
EpiControl
AF:
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 submitter | clinical testing | GeneDx | Nov 02, 2020 | 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) - |
Non-small cell lung carcinoma Other:1
not provided, no classification provided | literature only | Database of Curated Mutations (DoCM) | Mar 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;.
REVEL
Benign
Sift
Uncertain
D;D;.;.
Sift4G
Pathogenic
D;D;D;.
Polyphen
0.91
.;P;.;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at