rs1799801

Positions:

chr16-13948101-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005236.3(ERCC4):c.2505T>C(p.Ser835Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,896 control chromosomes in the GnomAD database, including 66,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5045 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61143 hom. )

Consequence

ERCC4
NM_005236.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-13948101-T-C is Benign according to our data. Variant chr16-13948101-T-C is described in ClinVar as [Benign]. Clinvar id is 129007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-13948101-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC4	NM_005236.3 link	c.2505T>C	p.Ser835Ser	synonymous_variant	11/11	ENST00000311895.8	NP_005227.1	Q92889-1A0A1W1GSK9
ERCC4	XM_011522424.4 link	c.2643T>C	p.Ser881Ser	synonymous_variant	12/12		XP_011520726.1	A0A804HKF9
ERCC4	XM_047433774.1 link	c.1716T>C	p.Ser572Ser	synonymous_variant	8/8		XP_047289730.1
ERCC4	XM_011522427.2 link	c.1155T>C	p.Ser385Ser	synonymous_variant	6/6		XP_011520729.1	B4DXD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 link	c.2505T>C	p.Ser835Ser	synonymous_variant	11/11	1	NM_005236.3	ENSP00000310520.7		Q92889-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37968

AN:

151962

Hom.:

5036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.290

GnomAD3 exomes

AF:

0.272

AC:

68347

AN:

251224

Hom.:

9533

AF XY:

0.279

AC XY:

37880

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.312

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.287

AC:

419607

AN:

1461816

Hom.:

61143

Cov.:

AF XY:

0.290

AC XY:

210714

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.250

AC:

38007

AN:

152080

Hom.:

5045

Cov.:

AF XY:

0.248

AC XY:

18465

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.249

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.288

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.286

Hom.:

8249

Bravo

AF:

0.247

Asia WGS

AF:

0.304

AC:

1057

AN:

3478

EpiCase

AF:

0.305

EpiControl

AF:

0.299

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group F

Benign:3

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 26, 2019	- -

Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.13

DANN

Benign

0.45

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