Variant rs1799800 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.1905-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,430,286 control chromosomes in the GnomAD database, including 51,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4292 hom., cov: 33)

Exomes 𝑓: 0.27 ( 47307 hom. )

Consequence

ERCC4
NM_005236.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.64

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:

ERCC4 (HGNC:):

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 16-13944695-G-A is Benign according to our data. Variant chr16-13944695-G-A is described in ClinVar as [Benign]. Clinvar id is 1229533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ERCC4	NM_005236.3 linkuse as main transcript	c.1905-28G>A	intron_variant	ENST00000311895.8	NP_005227.1	Q92889-1A0A1W1GSK9
ERCC4	XM_011522424.4 linkuse as main transcript	c.2043-28G>A	intron_variant		XP_011520726.1	A0A804HKF9
ERCC4	XM_047433774.1 linkuse as main transcript	c.1116-28G>A	intron_variant		XP_047289730.1
ERCC4	XM_011522427.2 linkuse as main transcript	c.555-28G>A	intron_variant		XP_011520729.1	B4DXD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 linkuse as main transcript	c.1905-28G>A		intron_variant		1	NM_005236.3	ENSP00000310520.7		Q92889-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34854

AN:

151938

Hom.:

4289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.240

AC:

60105

AN:

250470

Hom.:

7489

AF XY:

0.247

AC XY:

33458

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.267

AC:

340803

AN:

1278230

Hom.:

47307

Cov.:

AF XY:

0.268

AC XY:

173139

AN XY:

645940

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.229

AC:

34874

AN:

152056

Hom.:

4292

Cov.:

AF XY:

0.227

AC XY:

16851

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.265

Hom.:

1019

Bravo

AF:

0.223

Asia WGS

AF:

0.271

AC:

944

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Jan 10, 2019	- -

XFE progeroid syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Fanconi anemia complementation group Q

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Xeroderma pigmentosum, group F

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

-0.92

CADD

Benign

0.11

DANN

Benign

0.28

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