chr3-14159900-T-G

Variant names:

• chr3-14159900-T-G
• rs3731124
• NM_004628.5:c.901-70A>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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.171
• Publications: 10 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=-0.81).
• BP6: Variant 3-14159900-T-G is Benign according to our data. Variant chr3-14159900-T-G is described in ClinVar as Benign. ClinVar VariationId is 1291862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
XPC	NM_004628.5	c.901-70A>C		intron_variant	Intron 7 of 15	ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.901-70A>C		intron_variant	Intron 7 of 15	1	NM_004628.5	ENSP00000285021.8

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

African (AFR) AF: 0.0947 AC: 2775 AN: 29294

American (AMR) AF: 0.281 AC: 9899 AN: 35242

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5222 AN: 24486

East Asian (EAS) AF: 0.0379 AC: 1331 AN: 35088

South Asian (SAS) AF: 0.256 AC: 19627 AN: 76578

European-Finnish (FIN) AF: 0.214 AC: 9996 AN: 46692

Middle Eastern (MID) AF: 0.150 AC: 764 AN: 5096

European-Non Finnish (NFE) AF: 0.248 AC: 243963 AN: 982996

Other (OTH) AF: 0.216 AC: 11756 AN: 54440

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

African (AFR) AF: 0.0956 AC: 3969 AN: 41522

American (AMR) AF: 0.217 AC: 3314 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3472

East Asian (EAS) AF: 0.0412 AC: 213 AN: 5170

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2218 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16261 AN: 67998

Other (OTH) AF: 0.190 AC: 400 AN: 2110

Alfa AF: 0.225 Hom.: 935

Bravo AF: 0.184

Asia WGS AF: 0.179 AC: 620 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 10, 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	-0.81
CADD	Benign	4.2
DANN	Benign	0.51
PhyloP100		0.17
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: rs3731124; hg19: chr3-14201400;