3-14151668-C-T

Position:

• chr3-14151668-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004628.5(XPC):​c.2115+667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,962 control chromosomes in the GnomAD database, including 18,518 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (18518 hom., cov: 31)
  • Exomes 𝑓: 0.27 (0 hom.)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPC	NM_004628.5	c.2115+667G>A		intron_variant		ENST00000285021.12	NP_004619.3
XPC-AS1	XR_001740603.2	n.1868C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.2115+667G>A		intron_variant		1	NM_004628.5	ENSP00000285021	P1
XPC-AS1	ENST00000627116.2	n.456+1671C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74497 AN: 151822 Hom.: 18500 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.273 AC: 6 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.313 AC XY: 5 AN XY: 16

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.491 AC: 74570 AN: 151940 Hom.: 18518 Cov.: 31 AF XY: 0.490 AC XY: 36366 AN XY: 74232

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.499

Alfa AF: 0.485 Hom.: 4156

Bravo AF: 0.499

Asia WGS AF: 0.402 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.73

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: rs2607737; hg19: chr3-14193168;