rs3117
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000082.4(ERCC8):c.*105T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 915,126 control chromosomes in the GnomAD database, including 63,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.36 ( 10479 hom., cov: 31)
Exomes 𝑓: 0.36 ( 53004 hom. )
Consequence
ERCC8
NM_000082.4 3_prime_UTR
NM_000082.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.661
Genes affected
ERCC8 (HGNC:3439): (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 5-60874510-A-G is Benign according to our data. Variant chr5-60874510-A-G is described in ClinVar as [Benign]. Clinvar id is 354011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC8 | NM_000082.4 | c.*105T>C | 3_prime_UTR_variant | 12/12 | ENST00000676185.1 | ||
ERCC8 | NM_001007233.3 | c.*105T>C | 3_prime_UTR_variant | 13/13 | |||
ERCC8 | NM_001290285.2 | c.*105T>C | 3_prime_UTR_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC8 | ENST00000676185.1 | c.*105T>C | 3_prime_UTR_variant | 12/12 | NM_000082.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.364 AC: 55224AN: 151816Hom.: 10463 Cov.: 31
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GnomAD4 exome AF: 0.363 AC: 277011AN: 763192Hom.: 53004 Cov.: 10 AF XY: 0.364 AC XY: 144467AN XY: 397414
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GnomAD4 genome ? AF: 0.364 AC: 55271AN: 151934Hom.: 10479 Cov.: 31 AF XY: 0.360 AC XY: 26757AN XY: 74270
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Cockayne syndrome type 1 Benign:1
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. - |
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