rs1047768

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000123.4(ERCC5):c.138T>C(p.His46His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,696 control chromosomes in the GnomAD database, including 273,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26664 hom., cov: 32)

Exomes 𝑓: 0.57 ( 246624 hom. )

Consequence

ERCC5
NM_000123.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.00400

Publications

142 publications found

Variant links:

Genes affected

ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

ERCC5 links:

BIVM-ERCC5 (HGNC:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]

BIVM-ERCC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 13-102852167-T-C is Benign according to our data. Variant chr13-102852167-T-C is described in ClinVar as Benign. ClinVar VariationId is 129009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4 link	c.138T>C	p.His46His	synonymous_variant	Exon 2 of 15	ENST00000652225.2	NP_000114.3	P28715-1
BIVM-ERCC5	NM_001204425.2 link	c.1500T>C	p.His500His	synonymous_variant	Exon 10 of 23		NP_001191354.2	R4GMW8Q59FZ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERCC5	ENST00000652225.2 link	c.138T>C	p.His46His	synonymous_variant	Exon 2 of 15		NM_000123.4	ENSP00000498881.2	P28715-1
BIVM-ERCC5	ENST00000639435.1 link	c.1500T>C	p.His500His	synonymous_variant	Exon 12 of 25	5		ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1 link	c.813T>C	p.His271His	synonymous_variant	Exon 11 of 24	5		ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88613

AN:

151876

Hom.:

26615

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.623

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.596

Gnomad OTH

AF:

0.568

GnomAD2 exomes

AF:

0.520

AC:

130641

AN:

251366

AF XY:

0.527

show subpopulations

Gnomad AFR exome

AF:

0.662

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.619

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.574

AC:

839091

AN:

1461702

Hom.:

246624

Cov.:

AF XY:

0.573

AC XY:

416387

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.668

AC:

22379

AN:

33478

American (AMR)

AF:

0.310

AC:

13851

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

15066

AN:

26130

East Asian (EAS)

AF:

0.224

AC:

8872

AN:

39680

South Asian (SAS)

AF:

0.501

AC:

43205

AN:

86244

European-Finnish (FIN)

AF:

0.613

AC:

32755

AN:

53404

Middle Eastern (MID)

AF:

0.523

AC:

3017

AN:

5766

European-Non Finnish (NFE)

AF:

0.599

AC:

665792

AN:

1111904

Other (OTH)

AF:

0.566

AC:

34154

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19212

38424

57637

76849

96061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18010

36020

54030

72040

90050

<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:

0.584

AC:

88713

AN:

151994

Hom.:

26664

Cov.:

AF XY:

0.580

AC XY:

43078

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.665

AC:

27556

AN:

41442

American (AMR)

AF:

0.426

AC:

6506

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2049

AN:

3470

East Asian (EAS)

AF:

0.249

AC:

1289

AN:

5178

South Asian (SAS)

AF:

0.495

AC:

2384

AN:

4818

European-Finnish (FIN)

AF:

0.623

AC:

6552

AN:

10516

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.596

AC:

40504

AN:

67976

Other (OTH)

AF:

0.571

AC:

1204

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1818

3636

5454

7272

9090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.578

Hom.:

110292

Bravo

AF:

0.569

Asia WGS

AF:

0.406

AC:

1415

AN:

3478

EpiCase

AF:

0.584

EpiControl

AF:

0.586

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group G

Benign:3

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical 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. -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

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

-0.59

CADD

Benign

0.10

(source)

DANN

Benign

0.33

PhyloP100

-0.0040

Mutation Taster

=99/1

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