Genetic Variant ENST00000575156.5:c.*792G>T (chr16-13933094-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000575156.5(ERCC4):c.*792G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 377,386 control chromosomes in the GnomAD database, including 21,664 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 11095 hom., cov: 26)

Exomes 𝑓: 0.29 ( 10569 hom. )

Consequence

ERCC4
ENST00000575156.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

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:

ENSG00000262732 (HGNC:):

ENSG00000262732 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3 link	c.1102+809G>T	intron_variant	Intron 6 of 10	ENST00000311895.8	NP_005227.1	Q92889-1A0A1W1GSK9
ERCC4	XM_011522424.4 link	c.1240+809G>T	intron_variant	Intron 7 of 11		XP_011520726.1	A0A804HKF9
ERCC4	XM_047433774.1 link	c.313+809G>T	intron_variant	Intron 3 of 7		XP_047289730.1
ERCC4	XM_011522427.2 link	c.-249+690G>T	intron_variant	Intron 1 of 5		XP_011520729.1	B4DXD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 link	c.1102+809G>T		intron_variant	Intron 6 of 10	1	NM_005236.3	ENSP00000310520.7		Q92889-1

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

55173

AN:

148152

Hom.:

11069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.422

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.384

GnomAD3 exomes

AF:

0.253

AC:

14805

AN:

58628

Hom.:

2100

AF XY:

0.258

AC XY:

8186

AN XY:

31774

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.292

AC:

66871

AN:

229138

Hom.:

10569

Cov.:

AF XY:

0.291

AC XY:

38900

AN XY:

133584

show subpopulations

Gnomad4 AFR exome

AF:

0.471

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.360

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.373

AC:

55242

AN:

148248

Hom.:

11095

Cov.:

AF XY:

0.366

AC XY:

26332

AN XY:

71958

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.246

Hom.:

1026

Bravo

AF:

0.379

Asia WGS

AF:

0.307

AC:

1071

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.46

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over