rs2733534

chr3-14147262-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004628.5(XPC):c.2604+28C>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 1,588,642 control chromosomes in the GnomAD database, including 168,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13684 hom., cov: 32)
  • Exomes 𝑓: 0.46 (154687 hom.)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0280

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-14147262-G-C is Benign according to our data. Variant chr3-14147262-G-C is described in ClinVar as [Benign]. Clinvar id is 259470.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	UniProt
XPC	NM_004628.5	c.2604+28C>G		intron_variant		ENST00000285021.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPC	ENST00000285021.12	c.2604+28C>G		intron_variant		1	NM_004628.5	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62963 AN: 151908 Hom.: 13676 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0428

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.444

GnomAD3 exomes AF: 0.411 AC: 87089 AN: 212032 Hom.: 19181 AF XY: 0.411 AC XY: 46829 AN XY: 114038

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.0412

Gnomad SAS exome AF: 0.391

Gnomad FIN exome AF: 0.459

Gnomad NFE exome AF: 0.470

Gnomad OTH exome AF: 0.426

GnomAD4 exome AF: 0.456 AC: 655326 AN: 1436616 Hom.: 154687 Cov.: 31 AF XY: 0.454 AC XY: 323158 AN XY: 712294

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.0393

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.414 AC: 63012 AN: 152026 Hom.: 13684 Cov.: 32 AF XY: 0.412 AC XY: 30617 AN XY: 74342

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.0427

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.440

Alfa AF: 0.437 Hom.: 2736

Bravo AF: 0.409

Asia WGS AF: 0.250 AC: 867 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.5
Dann	Benign	0.71

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

Other links and lift over

dbSNP: rs2733534; hg19: chr3-14188762; COSMIC: COSV53203693; COSMIC: COSV53203693;