16-13920198-C-T

Position:

chr16-13920198-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005236.3(ERCC4):c.33C>T(p.Ala11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,607,076 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 19 hom., cov: 33)

Exomes 𝑓: 0.021 ( 379 hom. )

Consequence

ERCC4
NM_005236.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.10

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:

LOC105371093 (HGNC:):

LOC105371093 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=-0.73).

BP6

Variant 16-13920198-C-T is Benign according to our data. Variant chr16-13920198-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 240125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-13920198-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.11 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0136 (2074/152360) while in subpopulation NFE AF= 0.0229 (1557/68036). AF 95% confidence interval is 0.0219. There are 19 homozygotes in gnomad4. There are 913 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ERCC4	NM_005236.3 linkuse as main transcript	c.33C>T	p.Ala11=	synonymous_variant	1/11	ENST00000311895.8
LOC105371093	XR_007065000.1 linkuse as main transcript	n.82+6327G>A		intron_variant, non_coding_transcript_variant
ERCC4	XM_011522424.4 linkuse as main transcript	c.33C>T	p.Ala11=	synonymous_variant	1/12
LOC105371093	XR_007064999.1 linkuse as main transcript	n.82+6327G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC4	ENST00000311895.8 linkuse as main transcript	c.33C>T	p.Ala11=	synonymous_variant	1/11	1	NM_005236.3	P1	Q92889-1

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2068

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00562

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00856

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0229

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0128

AC:

3131

AN:

243880

Hom.:

AF XY:

0.0125

AC XY:

1668

AN XY:

132934

show subpopulations

Gnomad AFR exome

AF:

0.00470

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00758

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.00913

Gnomad NFE exome

AF:

0.0228

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.0206

AC:

29950

AN:

1454716

Hom.:

379

Cov.:

AF XY:

0.0197

AC XY:

14266

AN XY:

724034

show subpopulations

Gnomad4 AFR exome

AF:

0.00436

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.00853

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0250

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0136

AC:

2074

AN:

152360

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

913

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00575

Gnomad4 AMR

AF:

0.00823

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00856

Gnomad4 NFE

AF:

0.0229

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0199

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0218

EpiControl

AF:

0.0179

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group F

Benign:2

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	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 12, 2016

- -

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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.0

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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