chr13-102872412-C-T

Position:

chr13-102872412-C-T

Variant summary

Our verdict is Benign. Variant got -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:8

Conservation

PhyloP100: -0.309

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:):

BIVM-ERCC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 255161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102872412-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4 linkuse as main transcript	c.2879+14C>T		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2 linkuse as main transcript	c.4241+14C>T		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2 linkuse as main transcript	c.2879+14C>T		intron_variant			NM_000123.4	ENSP00000498881	P1	P28715-1

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

GnomAD3 exomes

AF:

0.443

AC:

110813

AN:

249990

Hom.:

27148

AF XY:

0.457

AC XY:

61824

AN XY:

135168

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 SAS exome

AF:

0.442

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

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.445

Gnomad4 FIN exome

AF:

0.543

Gnomad4 NFE exome

AF:

0.560

Gnomad4 OTH exome

AF:

0.493

GnomAD4 genome

AF:

0.425

AC:

64691

AN:

152100

Hom.:

15544

Cov.:

AF XY:

0.425

AC XY:

31593

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.553

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.464

Hom.:

3911

Bravo

AF:

0.400

Asia WGS

AF:

0.315

AC:

1100

AN:

3478

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

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. -
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	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cerebrooculofacioskeletal syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.78

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