rs2020915

Positions:

chr13-102852300-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000123.4(ERCC5):c.264+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,613,432 control chromosomes in the GnomAD database, including 1,893 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 969 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 924 hom. )

Consequence

ERCC5
NM_000123.4 splice_region, intron

Scores

Splicing: ADA: 0.00003571

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.577

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:

ERCC5 (HGNC:):

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=-0.79).

BP6

Variant 13-102852300-G-A is Benign according to our data. Variant chr13-102852300-G-A is described in ClinVar as [Benign]. Clinvar id is 255160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102852300-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 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.264+7G>A		splice_region_variant, intron_variant		ENST00000652225.2	NP_000114.3	P28715-1
BIVM-ERCC5	NM_001204425.2 linkuse as main transcript	c.1626+7G>A		splice_region_variant, intron_variant			NP_001191354.2	R4GMW8Q59FZ7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ERCC5	ENST00000652225.2 linkuse as main transcript	c.264+7G>A	splice_region_variant, intron_variant		NM_000123.4	ENSP00000498881.2	P28715-1
BIVM-ERCC5	ENST00000639435.1 linkuse as main transcript	c.1626+7G>A	splice_region_variant, intron_variant	5		ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1 linkuse as main transcript	c.939+7G>A	splice_region_variant, intron_variant	5		ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9393

AN:

152032

Hom.:

968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0166

AC:

4163

AN:

251112

Hom.:

414

AF XY:

0.0122

AC XY:

1660

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.00977

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000511

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.00665

AC:

9720

AN:

1461282

Hom.:

924

Cov.:

AF XY:

0.00589

AC XY:

4279

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.0111

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000501

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000284

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0618

AC:

9409

AN:

152150

Hom.:

969

Cov.:

AF XY:

0.0599

AC XY:

4460

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.0220

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0310

Hom.:

270

Bravo

AF:

0.0706

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Xeroderma pigmentosum, group G

Benign:1

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

-0.79

CADD

Benign

5.2

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

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