Genetic Variant NM_004628.5:c.901-70A>C (chr3-14159900-T-G) – ACMG Classification: Benign (-20 pts)

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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.171

Publications

10 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=-0.81).

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 link	c.901-70A>C		intron_variant	Intron 7 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.901-70A>C		intron_variant	Intron 7 of 15	1	NM_004628.5	ENSP00000285021.8		Q01831-1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28526

AN:

152060

Hom.:

3048

Cov.:

show subpopulations

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.:

AF XY:

0.237

AC XY:

151638

AN XY:

641072

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11331

22662

33994

45325

56656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8124

16248

24372

32496

40620

<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:

0.188

AC:

28537

AN:

152178

Hom.:

3050

Cov.:

AF XY:

0.187

AC XY:

13943

AN XY:

74416

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16261

AN:

67998

Other (OTH)

AF:

0.190

AC:

400

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1178

2356

3535

4713

5891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.225

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.2

(source)

DANN

Benign

0.51

PhyloP100

0.17

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

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