rs2733532

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004628.5(XPC):c.2605-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,548,762 control chromosomes in the GnomAD database, including 297,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.66 ( 32936 hom., cov: 27)

Exomes 𝑓: 0.61 ( 264361 hom. )

Consequence

XPC
NM_004628.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.605

Publications

20 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:

ENSG00000268279 (HGNC:):

ENSG00000268279 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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-14146199-T-C is Benign according to our data. Variant chr3-14146199-T-C is described in ClinVar as Benign. ClinVar VariationId is 259471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPC	NM_004628.5 link	c.2605-40A>G		intron_variant	Intron 15 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.2605-40A>G		intron_variant	Intron 15 of 15	1	NM_004628.5	ENSP00000285021.8		Q01831-1
ENSG00000268279	ENST00000608606.1 link	n.*198+516T>C		intron_variant	Intron 4 of 4	5		ENSP00000476275.1		V9GY05

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99151

AN:

151088

Hom.:

32886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.648

GnomAD2 exomes

AF:

0.640

AC:

110034

AN:

172046

AF XY:

0.635

show subpopulations

Gnomad AFR exome

AF:

0.751

Gnomad AMR exome

AF:

0.709

Gnomad ASJ exome

AF:

0.530

Gnomad EAS exome

AF:

0.648

Gnomad FIN exome

AF:

0.695

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.613

AC:

856984

AN:

1397556

Hom.:

264361

Cov.:

AF XY:

0.612

AC XY:

423760

AN XY:

692150

show subpopulations

African (AFR)

AF:

0.752

AC:

24144

AN:

32126

American (AMR)

AF:

0.705

AC:

26426

AN:

37502

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

13375

AN:

25260

East Asian (EAS)

AF:

0.623

AC:

23174

AN:

37220

South Asian (SAS)

AF:

0.647

AC:

52235

AN:

80686

European-Finnish (FIN)

AF:

0.692

AC:

29363

AN:

42418

Middle Eastern (MID)

AF:

0.461

AC:

2427

AN:

5268

European-Non Finnish (NFE)

AF:

0.603

AC:

650433

AN:

1078736

Other (OTH)

AF:

0.607

AC:

35407

AN:

58340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

16805

33611

50416

67222

84027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17872

35744

53616

71488

89360

<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:

0.657

AC:

99276

AN:

151206

Hom.:

32936

Cov.:

AF XY:

0.662

AC XY:

48824

AN XY:

73804

show subpopulations

African (AFR)

AF:

0.746

AC:

30713

AN:

41174

American (AMR)

AF:

0.676

AC:

10297

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

1849

AN:

3466

East Asian (EAS)

AF:

0.642

AC:

3259

AN:

5078

South Asian (SAS)

AF:

0.660

AC:

3127

AN:

4736

European-Finnish (FIN)

AF:

0.702

AC:

7381

AN:

10518

Middle Eastern (MID)

AF:

0.490

AC:

143

AN:

292

European-Non Finnish (NFE)

AF:

0.598

AC:

40506

AN:

67714

Other (OTH)

AF:

0.651

AC:

1363

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1634

3267

4901

6534

8168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.614

Hom.:

7227

Bravo

AF:

0.659

Asia WGS

AF:

0.684

AC:

2376

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Xeroderma pigmentosum, group C

Benign:2

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

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

-0.88

CADD

Benign

2.9

(source)

DANN

Benign

0.73

PhyloP100

-0.60

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over