rs2020958
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_005236.3(ERCC4):āc.1884A>Gā(p.Glu628=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,612,194 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.013 ( 44 hom., cov: 32)
Exomes š: 0.0013 ( 43 hom. )
Consequence
ERCC4
NM_005236.3 synonymous
NM_005236.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.990
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 16-13937838-A-G is Benign according to our data. Variant chr16-13937838-A-G is described in ClinVar as [Benign]. Clinvar id is 317817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-13937838-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.99 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1980/152304) while in subpopulation AFR AF= 0.0445 (1851/41566). AF 95% confidence interval is 0.0428. There are 44 homozygotes in gnomad4. There are 936 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 44 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.1884A>G | p.Glu628= | synonymous_variant | 9/11 | ENST00000311895.8 | |
ERCC4 | XM_011522424.4 | c.2022A>G | p.Glu674= | synonymous_variant | 10/12 | ||
ERCC4 | XM_047433774.1 | c.1095A>G | p.Glu365= | synonymous_variant | 6/8 | ||
ERCC4 | XM_011522427.2 | c.534A>G | p.Glu178= | synonymous_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.1884A>G | p.Glu628= | synonymous_variant | 9/11 | 1 | NM_005236.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0130 AC: 1974AN: 152186Hom.: 44 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1974
AN:
152186
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00338 AC: 849AN: 251268Hom.: 9 AF XY: 0.00230 AC XY: 313AN XY: 135840
GnomAD3 exomes
AF:
AC:
849
AN:
251268
Hom.:
AF XY:
AC XY:
313
AN XY:
135840
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00132 AC: 1933AN: 1459890Hom.: 43 Cov.: 30 AF XY: 0.00112 AC XY: 817AN XY: 726404
GnomAD4 exome
AF:
AC:
1933
AN:
1459890
Hom.:
Cov.:
30
AF XY:
AC XY:
817
AN XY:
726404
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0130 AC: 1980AN: 152304Hom.: 44 Cov.: 32 AF XY: 0.0126 AC XY: 936AN XY: 74468
GnomAD4 genome
?
AF:
AC:
1980
AN:
152304
Hom.:
Cov.:
32
AF XY:
AC XY:
936
AN XY:
74468
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
7
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4
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 | 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 | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
ERCC4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 04, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at