rs1106087

Variant names:

• chr3-14166208-C-A
• rs1106087
• NM_004628.5:c.622-623G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-14166208-C-A
• chr3-14166208-C-G
• chr3-14166208-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004628.5(XPC):​c.622-623G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,032 control chromosomes in the GnomAD database, including 4,107 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 0.21 (4107 hom., cov: 31)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPC	NM_004628.5	c.622-623G>T		intron_variant	Intron 5 of 15	ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.622-623G>T		intron_variant	Intron 5 of 15	1	NM_004628.5	ENSP00000285021.8

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32607 AN: 151914 Hom.: 4111 Cov.: 31

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.215 AC: 32614 AN: 152032 Hom.: 4107 Cov.: 31 AF XY: 0.219 AC XY: 16310 AN XY: 74314

African (AFR) AF: 0.0907 AC: 3763 AN: 41496

American (AMR) AF: 0.241 AC: 3679 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1872 AN: 5152

South Asian (SAS) AF: 0.200 AC: 960 AN: 4810

European-Finnish (FIN) AF: 0.367 AC: 3869 AN: 10556

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16735 AN: 67954

Other (OTH) AF: 0.244 AC: 515 AN: 2108

Alfa AF: 0.208 Hom.: 1912

Bravo AF: 0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.65
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1106087; hg19: chr3-14207708;