rs1870134

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.46C>G(p.Leu16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,612,914 control chromosomes in the GnomAD database, including 1,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L16L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.022 ( 209 hom., cov: 33)

Exomes 𝑓: 0.016 ( 1382 hom. )

Consequence

XPC
NM_004628.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -1.25

Publications

37 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 Gene-Disease associations (from GenCC):

xeroderma pigmentosum group C
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Genomics England PanelApp, ClinGen, G2P
xeroderma pigmentosum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

XPC 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 (MetaRNN=0.0032751262).

BP6

Variant 3-14178523-G-C is Benign according to our data. Variant chr3-14178523-G-C is described in ClinVar as Benign. ClinVar VariationId is 135465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 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	HGVSp	Effect	Exon Rank	Protein	UniProt
XPC	NM_004628.5	MANE Select	c.46C>G	p.Leu16Val	missense	Exon 1 of 16	NP_004619.3
XPC	NM_001354727.2		c.46C>G	p.Leu16Val	missense	Exon 1 of 16	NP_001341656.1	A0ABB0MVJ4
XPC	NM_001354729.2		c.46C>G	p.Leu16Val	missense	Exon 1 of 16	NP_001341658.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XPC	ENST00000285021.12	TSL:1 MANE Select	c.46C>G	p.Leu16Val	missense	Exon 1 of 16	ENSP00000285021.8	Q01831-1
XPC	ENST00000476581.6	TSL:1	n.46C>G		non_coding_transcript_exon	Exon 1 of 15	ENSP00000424548.1	Q01831-3
XPC	ENST00000850575.1		c.46C>G	p.Leu16Val	missense	Exon 1 of 16	ENSP00000520865.1	A0ABB0MVJ4

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3353

AN:

152266

Hom.:

208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00492

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0917

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.0374

Gnomad FIN

AF:

0.00828

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00441

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.0419

AC:

10341

AN:

246582

AF XY:

0.0372

show subpopulations

Gnomad AFR exome

AF:

0.00416

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.00361

Gnomad EAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0159

AC:

23236

AN:

1460530

Hom.:

1382

Cov.:

AF XY:

0.0158

AC XY:

11494

AN XY:

726614

show subpopulations

African (AFR)

AF:

0.00365

AC:

122

AN:

33460

American (AMR)

AF:

0.122

AC:

5448

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00395

AC:

103

AN:

26096

East Asian (EAS)

AF:

0.215

AC:

8524

AN:

39684

South Asian (SAS)

AF:

0.0300

AC:

2584

AN:

86230

European-Finnish (FIN)

AF:

0.0115

AC:

607

AN:

52722

Middle Eastern (MID)

AF:

0.00937

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00401

AC:

4460

AN:

1111544

Other (OTH)

AF:

0.0221

AC:

1334

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1296

2593

3889

5186

6482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.0221

AC:

3361

AN:

152384

Hom.:

209

Cov.:

AF XY:

0.0252

AC XY:

1880

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.00493

AC:

205

AN:

41596

American (AMR)

AF:

0.0918

AC:

1405

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.217

AC:

1123

AN:

5186

South Asian (SAS)

AF:

0.0374

AC:

181

AN:

4834

European-Finnish (FIN)

AF:

0.00828

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00442

AC:

301

AN:

68036

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

162

324

485

647

809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.00496

Hom.:

Bravo

AF:

0.0291

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00434

AC:

ESP6500EA

AF:

0.00522

AC:

ExAC

AF:

0.0369

AC:

4455

Asia WGS

AF:

0.117

AC:

407

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00450

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (4)

Xeroderma pigmentosum, group C (2)

Xeroderma pigmentosum group A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.13

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.051

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

-1.3

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.16

REVEL

Benign

0.051

Sift

Benign

0.24

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.028

MPC

0.12

ClinPred

0.0086

GERP RS

-4.0

PromoterAI

-0.080

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.035

Mutation Taster

=295/5

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over