rs4150360

Variant names:

Variant summary

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

The NM_000123.4(ERCC5):c.2879+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,613,166 control chromosomes in the GnomAD database, including 221,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15544 hom., cov: 32)

Exomes 𝑓: 0.52 ( 205807 hom. )

Consequence

ERCC5
NM_000123.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.309

Publications

19 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 13-102872412-C-T is Benign according to our data. Variant chr13-102872412-C-T is described in ClinVar as Benign. ClinVar VariationId is 255161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4 link	c.2879+14C>T		intron_variant	Intron 13 of 14	ENST00000652225.2	NP_000114.3	P28715-1
BIVM-ERCC5	NM_001204425.2 link	c.4241+14C>T		intron_variant	Intron 21 of 22		NP_001191354.2	R4GMW8Q59FZ7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERCC5	ENST00000652225.2 link	c.2879+14C>T	intron_variant	Intron 13 of 14		NM_000123.4	ENSP00000498881.2	P28715-1
BIVM-ERCC5	ENST00000639435.1 link	c.4241+14C>T	intron_variant	Intron 23 of 24	5		ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1 link	c.3554+14C>T	intron_variant	Intron 22 of 23	5		ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64655

AN:

151982

Hom.:

15533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.427

GnomAD2 exomes

AF:

0.443

AC:

110813

AN:

249990

AF XY:

0.457

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.546

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.521

AC:

760704

AN:

1461066

Hom.:

205807

Cov.:

AF XY:

0.520

AC XY:

377970

AN XY:

726780

show subpopulations

African (AFR)

AF:

0.221

AC:

7397

AN:

33466

American (AMR)

AF:

0.263

AC:

11749

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

13702

AN:

26120

East Asian (EAS)

AF:

0.160

AC:

6341

AN:

39690

South Asian (SAS)

AF:

0.445

AC:

38326

AN:

86184

European-Finnish (FIN)

AF:

0.543

AC:

29010

AN:

53398

Middle Eastern (MID)

AF:

0.433

AC:

2497

AN:

5766

European-Non Finnish (NFE)

AF:

0.560

AC:

621925

AN:

1111452

Other (OTH)

AF:

0.493

AC:

29757

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

17847

35694

53541

71388

89235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17172

34344

51516

68688

85860

<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:

0.425

AC:

64691

AN:

152100

Hom.:

15544

Cov.:

AF XY:

0.425

AC XY:

31593

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.232

AC:

9624

AN:

41498

American (AMR)

AF:

0.354

AC:

5407

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1879

AN:

3470

East Asian (EAS)

AF:

0.185

AC:

959

AN:

5182

South Asian (SAS)

AF:

0.437

AC:

2099

AN:

4806

European-Finnish (FIN)

AF:

0.553

AC:

5845

AN:

10564

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.549

AC:

37330

AN:

67980

Other (OTH)

AF:

0.431

AC:

912

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1783

3566

5350

7133

8916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.458

Hom.:

3930

Bravo

AF:

0.400

Asia WGS

AF:

0.315

AC:

1100

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group G

Benign:4

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control 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. -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:3

Nov 11, 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:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cerebrooculofacioskeletal syndrome 3

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

-0.66

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

-0.31

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over