Variant rs2733532 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_004628.5(XPC):c.2605-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,548,762 control chromosomes in the GnomAD database, including 297,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.66 ( 32936 hom., cov: 27)

Exomes 𝑓: 0.61 ( 264361 hom. )

Consequence

XPC
NM_004628.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.605

Variant links:

Genes affected

XPC (HGNC:12816): (XPC complex subunit, DNA damage recognition and repair factor) The protein encoded by this gene is a key component of the XPC complex, which plays an important role in the early steps of global genome nucleotide excision repair (NER). The encoded protein is important for damage sensing and DNA binding, and shows a preference for single-stranded DNA. Mutations in this gene or some other NER components can result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]

XPC links:

ENSG00000268279 (HGNC:):

ENSG00000268279 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-14146199-T-C is Benign according to our data. Variant chr3-14146199-T-C is described in ClinVar as [Benign]. Clinvar id is 259471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPC	NM_004628.5 linkuse as main transcript	c.2605-40A>G		intron_variant		ENST00000285021.12	NP_004619.3	Q01831-1X5DRB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12 linkuse as main transcript	c.2605-40A>G		intron_variant		1	NM_004628.5	ENSP00000285021.8		Q01831-1
ENSG00000268279	ENST00000608606.1 linkuse as main transcript	n.*198+516T>C		intron_variant		5		ENSP00000476275.1		V9GY05

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99151

AN:

151088

Hom.:

32886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.648

GnomAD3 exomes

AF:

0.640

AC:

110034

AN:

172046

Hom.:

35282

AF XY:

0.635

AC XY:

58833

AN XY:

92710

show subpopulations

Gnomad AFR exome

AF:

0.751

Gnomad AMR exome

AF:

0.709

Gnomad ASJ exome

AF:

0.530

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.648

Gnomad FIN exome

AF:

0.695

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.613

AC:

856984

AN:

1397556

Hom.:

264361

Cov.:

AF XY:

0.612

AC XY:

423760

AN XY:

692150

show subpopulations

Gnomad4 AFR exome

AF:

0.752

Gnomad4 AMR exome

AF:

0.705

Gnomad4 ASJ exome

AF:

0.529

Gnomad4 EAS exome

AF:

0.623

Gnomad4 SAS exome

AF:

0.647

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.603

Gnomad4 OTH exome

AF:

0.607

GnomAD4 genome

AF:

0.657

AC:

99276

AN:

151206

Hom.:

32936

Cov.:

AF XY:

0.662

AC XY:

48824

AN XY:

73804

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.676

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.642

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.702

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.651

Alfa

AF:

0.614

Hom.:

7227

Bravo

AF:

0.659

Asia WGS

AF:

0.684

AC:

2376

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Jan 10, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Xeroderma pigmentosum group A

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Xeroderma pigmentosum, group C

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

-0.88

CADD

Benign

2.9

DANN

Benign

0.73

BranchPoint Hunter

3.0

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