rs25487
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1
The NM_006297(XRCC1):c.1196A>G(p.Gln399Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152018 control chromosomes in the gnomAD Genomes database, including 39012 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).
Frequency
Genomes: 𝑓 0.71 ( 39012 hom., cov: 33)
Exomes 𝑓: 0.68 ( 58636 hom. )
Consequence
XRCC1
NM_006297 missense
NM_006297 missense
Scores
1
14
Clinical Significance
Conservation
PhyloP100: 1.98
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=6.525281E-7).
BP6
?
Variant 19:43551574-T>C is Benign according to our data. Variant chr19-43551574-T-C is described in ClinVar as [drug_response]. Clinvar id is 225976. Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Benign=2, drug_response=1}.
BA1
?
GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XRCC1 | NM_006297.3 | c.1196A>G | p.Gln399Arg | missense_variant | 10/17 | ENST00000262887.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC1 | ENST00000262887.10 | c.1196A>G | p.Gln399Arg | missense_variant | 10/17 | 1 | NM_006297.3 | P1 | |
XRCC1 | ENST00000543982.5 | c.1103A>G | p.Gln368Arg | missense_variant | 9/16 | 2 | |||
XRCC1 | ENST00000597811.5 | c.*310A>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.711 AC: 108110AN: 152018Hom.: 39012 Cov.: 33
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GnomAD3 exomes AF: 0.681 AC: 170473AN: 250468Hom.: 58636 AF XY: 0.673 AC XY: 91132AN XY: 135456
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GnomAD4 exome AF: 0.652 AC: 952451AN: 1460968Hom.: 312387 AF XY: 0.652 AC XY: 473566AN XY: 726870
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ClinVar
Significance: drug response
Submissions summary: Benign:2Other:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Spinocerebellar ataxia, autosomal recessive 26 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2020 | This variant is associated with the following publications: (PMID: 21427728, 15113441, 19481337, 11782372, 23479765, 14630517, 21843798, 22053659, 22951806, 24176953, 22224629, 22106831, 23360319, 21987112, 21928248, 18641418, 22193858, 19012493, 22525558, 22712837, 19880550, 22302399, 22983827, 21617750, 20431719, 23499241, 19465687, 20385586, 18357393, 21647176, 19051060, 23055018, 17961713, 22868082, 22568010, 19428062, 11104903, 24205020) - |
Platinum compounds response - Efficacy Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 2B: Variants in Level 2B clinical annotations are not in PharmGKB’s Tier 1 VIPs. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2B clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0
.;B
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Find out SpliceAI and Pangolin per-transcript scores at