rs1047768

Positions:

Variant summary

Our verdict is Benign. Variant got -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:7

Conservation

PhyloP100: -0.00400

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 made for transcript

Verdict is Benign. Variant got -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 id is 129009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102852167-T-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4 link	c.138T>C	p.His46His	synonymous_variant	2/15	ENST00000652225.2	NP_000114.3	P28715-1
BIVM-ERCC5	NM_001204425.2 link	c.1500T>C	p.His500His	synonymous_variant	10/23		NP_001191354.2	R4GMW8Q59FZ7

Ensembl

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

GnomAD3 exomes

AF:

0.520

AC:

130641

AN:

251366

Hom.:

36398

AF XY:

0.527

AC XY:

71638

AN XY:

135852

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 SAS exome

AF:

0.498

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

Gnomad4 AFR exome

AF:

0.668

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.577

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.501

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.566

GnomAD4 genome

AF:

0.584

AC:

88713

AN:

151994

Hom.:

26664

Cov.:

AF XY:

0.580

AC XY:

43078

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.590

Gnomad4 EAS

AF:

0.249

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.623

Gnomad4 NFE

AF:

0.596

Gnomad4 OTH

AF:

0.571

Alfa

AF:

0.578

Hom.:

50731

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Xeroderma pigmentosum, group G

Benign:2

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.10

DANN

Benign

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over