rs2296148

Positions:

chr13-102846195-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.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,310,150 control chromosomes in the GnomAD database, including 1,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 555 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1279 hom. )

Consequence

ERCC5
NM_000123.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.40

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=-0.62).

BP6

Variant 13-102846195-C-T is Benign according to our data. Variant chr13-102846195-C-T is described in ClinVar as [Benign]. Clinvar id is 310910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC5	NM_000123.4 linkuse as main transcript	c.-72C>T		5_prime_UTR_variant	1/15	ENST00000652225.2
BIVM-ERCC5	NM_001204425.2 linkuse as main transcript	c.1451-5923C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC5	ENST00000652225.2 linkuse as main transcript	c.-72C>T		5_prime_UTR_variant	1/15		NM_000123.4	P1	P28715-1

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

10817

AN:

152046

Hom.:

551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0363

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0527

Gnomad SAS

AF:

0.0516

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0422

Gnomad OTH

AF:

0.0728

GnomAD4 exome

AF:

0.0413

AC:

47815

AN:

1157986

Hom.:

1279

Cov.:

AF XY:

0.0414

AC XY:

24114

AN XY:

582296

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0280

Gnomad4 ASJ exome

AF:

0.0404

Gnomad4 EAS exome

AF:

0.0589

Gnomad4 SAS exome

AF:

0.0480

Gnomad4 FIN exome

AF:

0.0707

Gnomad4 NFE exome

AF:

0.0353

Gnomad4 OTH exome

AF:

0.0469

GnomAD4 genome

AF:

0.0713

AC:

10847

AN:

152164

Hom.:

555

Cov.:

AF XY:

0.0707

AC XY:

5262

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.0362

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.0529

Gnomad4 SAS

AF:

0.0520

Gnomad4 FIN

AF:

0.0720

Gnomad4 NFE

AF:

0.0422

Gnomad4 OTH

AF:

0.0716

Alfa

AF:

0.0571

Hom.:

122

Bravo

AF:

0.0706

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Xeroderma pigmentosum, group G

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.62

CADD

Benign

5.6

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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