Variant chr16-13950924-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005236.3(ERCC4):c.*2577C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 195,684 control chromosomes in the GnomAD database, including 5,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4462 hom., cov: 32)

Exomes 𝑓: 0.26 ( 1525 hom. )

Consequence

ERCC4
NM_005236.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.351

Variant links:

Genes affected

ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

ERCC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-13950924-C-A is Benign according to our data. Variant chr16-13950924-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 210952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ERCC4	NM_005236.3 linkuse as main transcript	c.*2577C>A	3_prime_UTR_variant	11/11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4 linkuse as main transcript	c.*2577C>A	3_prime_UTR_variant	12/12		XP_011520726.1
ERCC4	XM_011522427.2 linkuse as main transcript	c.*2577C>A	3_prime_UTR_variant	6/6		XP_011520729.1
ERCC4	XM_047433774.1 linkuse as main transcript	c.*2577C>A	3_prime_UTR_variant	8/8		XP_047289730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 linkuse as main transcript	c.*2577C>A		3_prime_UTR_variant	11/11	1	NM_005236.3	ENSP00000310520	P1	Q92889-1
ERCC4	ENST00000682617.1 linkuse as main transcript	c.*2577C>A		3_prime_UTR_variant	12/12			ENSP00000507912

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35470

AN:

151522

Hom.:

4458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.270

GnomAD4 exome

AF:

0.259

AC:

11416

AN:

44046

Hom.:

1525

Cov.:

AF XY:

0.266

AC XY:

5438

AN XY:

20476

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.234

AC:

35493

AN:

151638

Hom.:

4462

Cov.:

AF XY:

0.231

AC XY:

17135

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.187

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.246

Hom.:

572

Bravo

AF:

0.228

Asia WGS

AF:

0.268

AC:

934

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 11, 2015

- -

Xeroderma pigmentosum, group F

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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.64

DANN

Benign

0.59

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