dbSNP rs9653966: XPC:c.2034-514A>C (chr3-14152930-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004628.5(XPC):c.2034-514A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,408 control chromosomes in the GnomAD database, including 421 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 0.069 ( 421 hom., cov: 33)

Exomes 𝑓: 0.064 ( 0 hom. )

Consequence

XPC
NM_004628.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004628.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XPC	NM_004628.5	MANE Select	c.2034-514A>C	intron	N/A	NP_004619.3
XPC	NM_001354727.2		c.2028-514A>C	intron	N/A	NP_001341656.1	A0ABB0MVJ4
XPC	NM_001354729.2		c.2016-514A>C	intron	N/A	NP_001341658.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XPC	ENST00000285021.12	TSL:1 MANE Select	c.2034-514A>C	intron	N/A	ENSP00000285021.8	Q01831-1
XPC	ENST00000476581.6	TSL:1	n.*1487-514A>C	intron	N/A	ENSP00000424548.1	Q01831-3
XPC	ENST00000850575.1		c.2028-514A>C	intron	N/A	ENSP00000520865.1	A0ABB0MVJ4

Frequencies

GnomAD3 genomes

AF:

0.0693

AC:

10546

AN:

152150

Hom.:

418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0515

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0473

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.0115

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0820

Gnomad OTH

AF:

0.0612

GnomAD4 exome

AF:

0.0643

AC:

AN:

140

Hom.:

Cov.:

AF XY:

0.0294

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0833

AC:

AN:

108

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0694

AC:

10562

AN:

152268

Hom.:

421

Cov.:

AF XY:

0.0698

AC XY:

5197

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0514

AC:

2136

AN:

41534

American (AMR)

AF:

0.0473

AC:

723

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

268

AN:

3470

East Asian (EAS)

AF:

0.0116

AC:

AN:

5186

South Asian (SAS)

AF:

0.106

AC:

512

AN:

4832

European-Finnish (FIN)

AF:

0.104

AC:

1102

AN:

10616

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0820

AC:

5574

AN:

68012

Other (OTH)

AF:

0.0662

AC:

140

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

521

1043

1564

2086

2607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0806

Hom.:

Bravo

AF:

0.0612

Asia WGS

AF:

0.0720

AC:

253

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.047

(source)

DANN

Benign

0.70

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over