rs762521

Positions:

chr16-13920383-G-A

Variant summary

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

The NM_005236.3(ERCC4):c.207+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,554,340 control chromosomes in the GnomAD database, including 55,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4387 hom., cov: 33)

Exomes 𝑓: 0.27 ( 51362 hom. )

Consequence

ERCC4
NM_005236.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.67

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:

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=-0.72).

BP6

Variant 16-13920383-G-A is Benign according to our data. Variant chr16-13920383-G-A is described in ClinVar as [Benign]. Clinvar id is 259683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ERCC4	NM_005236.3 linkuse as main transcript	c.207+11G>A	intron_variant	ENST00000311895.8	NP_005227.1	Q92889-1A0A1W1GSK9
ERCC4	XM_011522424.4 linkuse as main transcript	c.207+11G>A	intron_variant		XP_011520726.1	A0A804HKF9
LOC105371093	XR_007064999.1 linkuse as main transcript	n.82+6142C>T	intron_variant
LOC105371093	XR_007065000.1 linkuse as main transcript	n.82+6142C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 linkuse as main transcript	c.207+11G>A		intron_variant		1	NM_005236.3	ENSP00000310520.7		Q92889-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35270

AN:

152074

Hom.:

4383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.250

AC:

40797

AN:

162972

Hom.:

5338

AF XY:

0.257

AC XY:

22955

AN XY:

89406

show subpopulations

Gnomad AFR exome

AF:

0.181

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.296

Gnomad EAS exome

AF:

0.263

Gnomad SAS exome

AF:

0.252

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.268

AC:

375739

AN:

1402148

Hom.:

51362

Cov.:

AF XY:

0.269

AC XY:

186949

AN XY:

694438

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.232

AC:

35291

AN:

152192

Hom.:

4387

Cov.:

AF XY:

0.229

AC XY:

17063

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.266

Hom.:

985

Bravo

AF:

0.226

Asia WGS

AF:

0.278

AC:

967

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

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

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.72

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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