Variant 3-14148768-G-C 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.2251-37C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,612,902 control chromosomes in the GnomAD database, including 170,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13681 hom., cov: 33)

Exomes 𝑓: 0.46 ( 157183 hom. )

Consequence

XPC
NM_004628.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.162

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:

XPC-AS1 (HGNC:55014): (XPC antisense RNA 1)

XPC-AS1 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=-0.77).

BP6

Variant 3-14148768-G-C is Benign according to our data. Variant chr3-14148768-G-C is described in ClinVar as [Benign]. Clinvar id is 259469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 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.2251-37C>G		intron_variant		ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12 linkuse as main transcript	c.2251-37C>G		intron_variant		1	NM_004628.5	ENSP00000285021	P1	Q01831-1
XPC-AS1	ENST00000627116.2 linkuse as main transcript	n.300+67G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62953

AN:

151978

Hom.:

13673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.472

Gnomad OTH

AF:

0.443

GnomAD3 exomes

AF:

0.412

AC:

102297

AN:

248198

Hom.:

22732

AF XY:

0.413

AC XY:

55633

AN XY:

134666

show subpopulations

Gnomad AFR exome

AF:

0.351

Gnomad AMR exome

AF:

0.422

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.0405

Gnomad SAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.456

AC:

665974

AN:

1460804

Hom.:

157183

Cov.:

AF XY:

0.453

AC XY:

329446

AN XY:

726518

show subpopulations

Gnomad4 AFR exome

AF:

0.355

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.430

Gnomad4 EAS exome

AF:

0.0394

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.483

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.414

AC:

63000

AN:

152098

Hom.:

13681

Cov.:

AF XY:

0.412

AC XY:

30600

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.0427

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.472

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.353

Hom.:

1572

Bravo

AF:

0.409

Asia WGS

AF:

0.249

AC:

865

AN:

3478

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

-0.77

CADD

Benign

5.7

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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