rs3731124

Positions:

• chr3-14159900-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004628.5(XPC):​c.901-70A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,442,090 control chromosomes in the GnomAD database, including 40,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3050 hom., cov: 32)
  • Exomes 𝑓: 0.24 (37667 hom.)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.171

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-14159900-T-G is Benign according to our data. Variant chr3-14159900-T-G is described in ClinVar as [Benign]. Clinvar id is 1291862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPC	NM_004628.5	c.901-70A>C		intron_variant		ENST00000285021.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPC	ENST00000285021.12	c.901-70A>C		intron_variant		1	NM_004628.5	P1
XPC-AS1	ENST00000627116.2	n.457-5976T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28526 AN: 152060 Hom.: 3048 Cov.: 32

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0413

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.237 AC: 305333 AN: 1289912 Hom.: 37667 Cov.: 19 AF XY: 0.237 AC XY: 151638 AN XY: 641072

Gnomad4 AFR exome AF: 0.0947

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.0379

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.188 AC: 28537 AN: 152178 Hom.: 3050 Cov.: 32 AF XY: 0.187 AC XY: 13943 AN XY: 74416

Gnomad4 AFR AF: 0.0956

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0412

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.190

Alfa AF: 0.228 Hom.: 932

Bravo AF: 0.184

Asia WGS AF: 0.179 AC: 620 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	4.2
DANN	Benign	0.51

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: rs3731124; hg19: chr3-14201400;