chr16-13920198-C-T
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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
NM_005236.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.10
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.33C>T | p.Ala11= | synonymous_variant | 1/11 | ENST00000311895.8 | |
LOC105371093 | XR_007065000.1 | n.82+6327G>A | intron_variant, non_coding_transcript_variant | ||||
ERCC4 | XM_011522424.4 | c.33C>T | p.Ala11= | synonymous_variant | 1/12 | ||
LOC105371093 | XR_007064999.1 | 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 | c.33C>T | p.Ala11= | synonymous_variant | 1/11 | 1 | NM_005236.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0136 AC: 2068AN: 152242Hom.: 19 Cov.: 33
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GnomAD3 exomes AF: 0.0128 AC: 3131AN: 243880Hom.: 42 AF XY: 0.0125 AC XY: 1668AN XY: 132934
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GnomAD4 exome AF: 0.0206 AC: 29950AN: 1454716Hom.: 379 Cov.: 35 AF XY: 0.0197 AC XY: 14266AN XY: 724034
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GnomAD4 genome AF: 0.0136 AC: 2074AN: 152360Hom.: 19 Cov.: 33 AF XY: 0.0123 AC XY: 913AN XY: 74508
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
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 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 | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at