rs3731127

Variant names:

• chr3-14158973-G-A
• rs3731127
• NM_004628.5:c.991-81C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-14158973-G-A
• chr3-14158973-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004628.5(XPC):​c.991-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 1,570,038 control chromosomes in the GnomAD database, including 2,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (173 hom., cov: 32)
  • Exomes 𝑓: 0.050 (2059 hom.)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-14158973-G-A is Benign according to our data. Variant chr3-14158973-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPC	NM_004628.5	c.991-81C>T		intron_variant	Intron 8 of 15	ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.991-81C>T		intron_variant	Intron 8 of 15	1	NM_004628.5	ENSP00000285021.8

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6010 AN: 151950 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.00955

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00977

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0364

GnomAD4 exome AF: 0.0504 AC: 71449 AN: 1417970 Hom.: 2059 AF XY: 0.0495 AC XY: 34914 AN XY: 706034

African (AFR) AF: 0.00732 AC: 237 AN: 32388

American (AMR) AF: 0.0186 AC: 787 AN: 42422

Ashkenazi Jewish (ASJ) AF: 0.0488 AC: 1250 AN: 25616

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39412

South Asian (SAS) AF: 0.0118 AC: 984 AN: 83640

European-Finnish (FIN) AF: 0.0618 AC: 2911 AN: 47134

Middle Eastern (MID) AF: 0.0227 AC: 94 AN: 4150

European-Non Finnish (NFE) AF: 0.0576 AC: 62488 AN: 1084382

Other (OTH) AF: 0.0458 AC: 2694 AN: 58826

GnomAD4 genome AF: 0.0395 AC: 6008 AN: 152068 Hom.: 173 Cov.: 32 AF XY: 0.0383 AC XY: 2848 AN XY: 74338

African (AFR) AF: 0.00952 AC: 395 AN: 41472

American (AMR) AF: 0.0282 AC: 431 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00957 AC: 46 AN: 4808

European-Finnish (FIN) AF: 0.0607 AC: 642 AN: 10570

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4253 AN: 67988

Other (OTH) AF: 0.0361 AC: 76 AN: 2108

Alfa AF: 0.0492 Hom.: 294

Bravo AF: 0.0345

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 31, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.6
DANN	Benign	0.35
PhyloP100		1.1
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: rs3731127; hg19: chr3-14200473;