rs4253013
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000124.4(ERCC6):c.411G>A(p.Leu137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 1,613,920 control chromosomes in the GnomAD database, including 8,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 1174 hom., cov: 33)
Exomes 𝑓: 0.081 ( 7669 hom. )
Consequence
ERCC6
NM_000124.4 synonymous
NM_000124.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.372
Genes affected
ERCC6 (HGNC:3438): (ERCC excision repair 6, chromatin remodeling factor) This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 10-49532554-C-T is Benign according to our data. Variant chr10-49532554-C-T is described in ClinVar as [Benign]. Clinvar id is 129019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-49532554-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.372 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC6 | NM_000124.4 | c.411G>A | p.Leu137= | synonymous_variant | 2/21 | ENST00000355832.10 | |
ERCC6 | NM_001277058.2 | c.411G>A | p.Leu137= | synonymous_variant | 2/6 | ENST00000447839.7 | |
ERCC6 | NM_001346440.2 | c.411G>A | p.Leu137= | synonymous_variant | 2/21 | ||
ERCC6 | NM_001277059.2 | c.411G>A | p.Leu137= | synonymous_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC6 | ENST00000355832.10 | c.411G>A | p.Leu137= | synonymous_variant | 2/21 | 1 | NM_000124.4 | P1 | |
ERCC6 | ENST00000447839.7 | c.411G>A | p.Leu137= | synonymous_variant | 2/6 | 2 | NM_001277058.2 |
Frequencies
GnomAD3 genomes ? AF: 0.103 AC: 15639AN: 152108Hom.: 1175 Cov.: 33
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GnomAD3 exomes AF: 0.128 AC: 32050AN: 251180Hom.: 3461 AF XY: 0.118 AC XY: 16077AN XY: 135786
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GnomAD4 exome AF: 0.0813 AC: 118907AN: 1461694Hom.: 7669 Cov.: 31 AF XY: 0.0810 AC XY: 58873AN XY: 727164
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GnomAD4 genome ? AF: 0.103 AC: 15652AN: 152226Hom.: 1174 Cov.: 33 AF XY: 0.108 AC XY: 8001AN XY: 74420
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ClinVar
Significance: Benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Claritas Genomics | Jun 11, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2018 | - - |
COFS syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Cerebrooculofacioskeletal syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Cockayne syndrome type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Cockayne syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
UV-sensitive syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
DE SANCTIS-CACCHIONE SYNDROME Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Macular degeneration Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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