Variant 19-43552260-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006297.3(XRCC1):c.839G>A(p.Arg280His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,605,884 control chromosomes in the GnomAD database, including 2,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R280C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.051 ( 262 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2406 hom. )

Consequence

XRCC1
NM_006297.3 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 1.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028283298).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3 linkuse as main transcript	c.839G>A	p.Arg280His	missense_variant	9/17	ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10 linkuse as main transcript	c.839G>A	p.Arg280His	missense_variant	9/17	1	NM_006297.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0512

AC:

7790

AN:

152010

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0827

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.0968

Gnomad SAS

AF:

0.0962

Gnomad FIN

AF:

0.0704

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.0589

GnomAD3 exomes

AF:

0.0711

AC:

16710

AN:

235054

Hom.:

723

AF XY:

0.0706

AC XY:

9015

AN XY:

127684

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.0607

Gnomad EAS exome

AF:

0.110

Gnomad SAS exome

AF:

0.0903

Gnomad FIN exome

AF:

0.0746

Gnomad NFE exome

AF:

0.0499

Gnomad OTH exome

AF:

0.0720

GnomAD4 exome

AF:

0.0529

AC:

76924

AN:

1453756

Hom.:

2406

Cov.:

AF XY:

0.0539

AC XY:

38963

AN XY:

722974

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.0612

Gnomad4 EAS exome

AF:

0.0917

Gnomad4 SAS exome

AF:

0.0887

Gnomad4 FIN exome

AF:

0.0740

Gnomad4 NFE exome

AF:

0.0453

Gnomad4 OTH exome

AF:

0.0574

GnomAD4 genome

AF:

0.0512

AC:

7787

AN:

152128

Hom.:

262

Cov.:

AF XY:

0.0551

AC XY:

4093

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.0827

Gnomad4 ASJ

AF:

0.0582

Gnomad4 EAS

AF:

0.0968

Gnomad4 SAS

AF:

0.0963

Gnomad4 FIN

AF:

0.0704

Gnomad4 NFE

AF:

0.0462

Gnomad4 OTH

AF:

0.0573

Alfa

AF:

0.0501

Hom.:

528

Bravo

AF:

0.0526

TwinsUK

AF:

0.0388

AC:

144

ALSPAC

AF:

0.0475

AC:

183

ESP6500AA

AF:

0.0318

AC:

140

ESP6500EA

AF:

0.0484

AC:

416

ExAC

AF:

0.0656

AC:

7950

Asia WGS

AF:

0.0930

AC:

323

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Laryngeal squamous cell carcinoma

Other:1

association, no assertion criteria provided

clinical testing

Department Of Otolaryngology, First Affiliated Hospital Of Xinjiang Medical University

Jun 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

.;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.53

.;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.036

Sift

Benign

0.12

T;T;.

Sift4G

Benign

0.40

T;T;T

Polyphen

0.95

.;P;.

Vest4

0.15

MPC

0.26

ClinPred

0.0072

GERP RS

-0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.32

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

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