Variant rs2307187 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_006297.3(XRCC1):c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,612,136 control chromosomes in the GnomAD database, including 271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.021 ( 48 hom., cov: 32)

Exomes 𝑓: 0.014 ( 223 hom. )

Consequence

XRCC1
NM_006297.3 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.46

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 19-43575459-G-A is Benign according to our data. Variant chr19-43575459-G-A is described in ClinVar as [Benign]. Clinvar id is 3060460.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0512 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.-1C>T		5_prime_UTR_variant	1/17	ENST00000262887.10
PINLYP	XM_047438830.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10 linkuse as main transcript	c.-1C>T		5_prime_UTR_variant	1/17	1	NM_006297.3	P1
	ENST00000600242.1 linkuse as main transcript	n.387G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3256

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0148

AC:

3686

AN:

249656

Hom.:

AF XY:

0.0151

AC XY:

2040

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.0371

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0241

GnomAD4 exome

AF:

0.0143

AC:

20942

AN:

1459824

Hom.:

223

Cov.:

AF XY:

0.0144

AC XY:

10432

AN XY:

726060

show subpopulations

Gnomad4 AFR exome

AF:

0.0421

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0257

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 FIN exome

AF:

0.00210

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0214

AC:

3262

AN:

152312

Hom.:

Cov.:

AF XY:

0.0210

AC XY:

1565

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0364

Gnomad4 AMR

AF:

0.0285

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0177

EpiControl

AF:

0.0177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XRCC1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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