rs2607755

Positions:

• chr3-14172533-T-C

Variant summary

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

The ENST00000285021.12(XPC):​c.299+334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,040 control chromosomes in the GnomAD database, including 13,681 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 0.41 (13681 hom., cov: 32)
• Consequence: XPC ENST00000285021.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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	c.299+334A>G		intron_variant		ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.299+334A>G		intron_variant		1	NM_004628.5	ENSP00000285021	P1
XPC	ENST00000476581.6	c.299+334A>G		intron_variant, NMD_transcript_variant		1		ENSP00000424548
XPC	ENST00000511155.1	c.281+334A>G		intron_variant		4		ENSP00000423867

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62983 AN: 151920 Hom.: 13672 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.415 AC: 63031 AN: 152040 Hom.: 13681 Cov.: 32 AF XY: 0.412 AC XY: 30602 AN XY: 74322

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.440

Alfa AF: 0.443 Hom.: 1863

Bravo AF: 0.409

Asia WGS AF: 0.251 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.24

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: rs2607755; hg19: chr3-14214033;