rs201126529
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_000082.4(ERCC8):c.482-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 1,610,122 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00039 ( 1 hom., cov: 30)
Exomes 𝑓: 0.00037 ( 1 hom. )
Consequence
ERCC8
NM_000082.4 splice_polypyrimidine_tract, intron
NM_000082.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.06
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 5-60903733-G-A is Benign according to our data. Variant chr5-60903733-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 254943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000395 (60/151918) while in subpopulation EAS AF= 0.00387 (20/5172). AF 95% confidence interval is 0.00256. There are 1 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC8 | NM_000082.4 | c.482-17C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000676185.1 | |||
ERCC8 | NM_001007233.3 | c.308-17C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
ERCC8 | NM_001007234.3 | c.482-17C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
ERCC8 | NM_001290285.2 | c.23-17C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC8 | ENST00000676185.1 | c.482-17C>T | splice_polypyrimidine_tract_variant, intron_variant | NM_000082.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000395 AC: 60AN: 151800Hom.: 1 Cov.: 30
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GnomAD3 exomes AF: 0.000551 AC: 138AN: 250412Hom.: 0 AF XY: 0.000539 AC XY: 73AN XY: 135410
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GnomAD4 exome AF: 0.000368 AC: 537AN: 1458204Hom.: 1 Cov.: 30 AF XY: 0.000360 AC XY: 261AN XY: 725532
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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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