Variant 19-43546043-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006297.3(XRCC1):c.1481+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,612,812 control chromosomes in the GnomAD database, including 136,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10827 hom., cov: 30)

Exomes 𝑓: 0.41 ( 125449 hom. )

Consequence

XRCC1
NM_006297.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0580

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-43546043-C-T is Benign according to our data. Variant chr19-43546043-C-T is described in ClinVar as [Benign]. Clinvar id is 1245878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3 link	c.1481+9G>A		intron_variant		ENST00000262887.10	NP_006288.2	P18887B2RCY5Q59HH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10 link	c.1481+9G>A		intron_variant		1	NM_006297.3	ENSP00000262887.5		P18887
XRCC1	ENST00000543982.5 link	c.1388+9G>A		intron_variant		2		ENSP00000443671.1		F5H8D7

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56207

AN:

151338

Hom.:

10821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.355

AC:

89171

AN:

250958

Hom.:

17611

AF XY:

0.365

AC XY:

49453

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.325

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.376

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.406

AC:

593905

AN:

1461356

Hom.:

125449

Cov.:

AF XY:

0.407

AC XY:

296148

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.374

Gnomad4 FIN exome

AF:

0.455

Gnomad4 NFE exome

AF:

0.432

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.371

AC:

56255

AN:

151456

Hom.:

10827

Cov.:

AF XY:

0.369

AC XY:

27311

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.400

Hom.:

8668

Bravo

AF:

0.349

Asia WGS

AF:

0.249

AC:

869

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.421

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 01, 2019	- -

Spinocerebellar ataxia, autosomal recessive 26

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.2

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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