rs3731116

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004628.5(XPC):c.780-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,603,448 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 5 hom. )

Consequence

XPC
NM_004628.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.384

Publications

0 publications found

Variant links:

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 links:

XPC-AS1 (HGNC:55014): (XPC antisense RNA 1)

XPC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 3-14164948-G-A is Benign according to our data. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14164948-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 259474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00313 (477/152290) while in subpopulation AFR AF = 0.011 (456/41562). AF 95% confidence interval is 0.0101. There are 0 homozygotes in GnomAd4. There are 229 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPC	NM_004628.5 link	c.780-15C>T		intron_variant	Intron 6 of 15	ENST00000285021.12	NP_004619.3	Q01831-1X5DRB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12 link	c.780-15C>T		intron_variant	Intron 6 of 15	1	NM_004628.5	ENSP00000285021.8		Q01831-1

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

477

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000816

AC:

195

AN:

239082

AF XY:

0.000739

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.000411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000527

GnomAD4 exome

AF:

0.000331

AC:

480

AN:

1451158

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

220

AN XY:

721294

show subpopulations

African (AFR)

AF:

0.0118

AC:

389

AN:

32828

American (AMR)

AF:

0.000585

AC:

AN:

42756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

39146

South Asian (SAS)

AF:

0.0000831

AC:

AN:

84236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1107348

Other (OTH)

AF:

0.000900

AC:

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00313

AC:

477

AN:

152290

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0110

AC:

456

AN:

41562

American (AMR)

AF:

0.00111

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00360

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group C

Benign:3

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Jul 27, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Xeroderma pigmentosum group A

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.7

(source)

DANN

Benign

0.77

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over