Variant rs2307177 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006297.3(XRCC1):c.1727A>C(p.Tyr576Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0123 in 1,613,906 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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. Y576N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.019 ( 42 hom., cov: 30)

Exomes 𝑓: 0.012 ( 156 hom. )

Consequence

XRCC1
NM_006297.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.06

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007240653).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0195 (2959/152036) while in subpopulation AFR AF= 0.0378 (1567/41428). AF 95% confidence interval is 0.0363. There are 42 homozygotes in gnomad4. There are 1402 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3 linkuse as main transcript	c.1727A>C	p.Tyr576Ser	missense_variant	16/17	ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10 linkuse as main transcript	c.1727A>C	p.Tyr576Ser	missense_variant	16/17	1	NM_006297.3	ENSP00000262887	P1
XRCC1	ENST00000543982.5 linkuse as main transcript	c.1634A>C	p.Tyr545Ser	missense_variant	15/16	2		ENSP00000443671

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2954

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0234

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0123

AC:

3100

AN:

251426

Hom.:

AF XY:

0.0126

AC XY:

1708

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0384

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.0186

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.0192

GnomAD4 exome

AF:

0.0116

AC:

16921

AN:

1461870

Hom.:

156

Cov.:

AF XY:

0.0116

AC XY:

8440

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0424

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.0192

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0195

AC:

2959

AN:

152036

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1402

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0378

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0148

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0225

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.0125

AC:

1514

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0136

EpiControl

AF:

0.0146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

0.0027

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

.;D

MetaRNN

Benign

0.0072

T;T

MutationTaster

Benign

1.0

N;N

Sift4G

Benign

0.11

T;T

Vest4

0.53

ClinPred

0.022

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over