Variant 19-43553075-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006297.3(XRCC1):c.618A>G(p.Pro206Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,576,866 control chromosomes in the GnomAD database, including 142,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12555 hom., cov: 32)

Exomes 𝑓: 0.42 ( 129985 hom. )

Consequence

XRCC1
NM_006297.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.46

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:

XRCC1 (HGNC:):

XRCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-43553075-T-C is Benign according to our data. Variant chr19-43553075-T-C is described in ClinVar as [Benign]. Clinvar id is 1684240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3 linkuse as main transcript	c.618A>G	p.Pro206Pro	synonymous_variant	7/17	ENST00000262887.10	NP_006288.2	P18887B2RCY5Q59HH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10 linkuse as main transcript	c.618A>G	p.Pro206Pro	synonymous_variant	7/17	1	NM_006297.3	ENSP00000262887.5		P18887

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60741

AN:

151870

Hom.:

12547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.390

GnomAD3 exomes

AF:

0.366

AC:

70755

AN:

193098

Hom.:

14204

AF XY:

0.375

AC XY:

38542

AN XY:

102866

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.389

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.420

AC:

598441

AN:

1424878

Hom.:

129985

Cov.:

AF XY:

0.421

AC XY:

296605

AN XY:

705218

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.455

Gnomad4 NFE exome

AF:

0.443

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

AF:

0.400

AC:

60793

AN:

151988

Hom.:

12555

Cov.:

AF XY:

0.397

AC XY:

29497

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.395

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.335

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.413

Hom.:

7591

Bravo

AF:

0.382

Asia WGS

AF:

0.258

AC:

904

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.068

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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