2-127257567-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000122.2(ERCC3):c.*29C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,612,784 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0070 ( 5 hom., cov: 32)
Exomes 𝑓: 0.011 ( 104 hom. )
Consequence
ERCC3
NM_000122.2 3_prime_UTR
NM_000122.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.347
Genes affected
ERCC3 (HGNC:3435): (ERCC excision repair 3, TFIIH core complex helicase subunit) This gene encodes an ATP-dependent DNA helicase that functions in nucleotide excision repair. The encoded protein is a subunit of basal transcription factor 2 (TFIIH) and, therefore, also functions in class II transcription. Mutations in this gene are associated with Xeroderma pigmentosum B, Cockayne's syndrome, and trichothiodystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 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=-0.9).
BP6
Variant 2-127257567-G-A is Benign according to our data. Variant chr2-127257567-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 331072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00702 (1069/152274) while in subpopulation NFE AF= 0.012 (816/68022). AF 95% confidence interval is 0.0113. There are 5 homozygotes in gnomad4. There are 496 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ERCC3 | NM_000122.2 | c.*29C>T | 3_prime_UTR_variant | 15/15 | ENST00000285398.7 | NP_000113.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERCC3 | ENST00000285398.7 | c.*29C>T | 3_prime_UTR_variant | 15/15 | 1 | NM_000122.2 | ENSP00000285398 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00703 AC: 1069AN: 152156Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00680 AC: 1709AN: 251422Hom.: 10 AF XY: 0.00674 AC XY: 916AN XY: 135872
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GnomAD4 exome AF: 0.0110 AC: 16017AN: 1460510Hom.: 104 Cov.: 31 AF XY: 0.0106 AC XY: 7720AN XY: 726560
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GnomAD4 genome AF: 0.00702 AC: 1069AN: 152274Hom.: 5 Cov.: 32 AF XY: 0.00666 AC XY: 496AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | ERCC3: BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 04, 2019 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Xeroderma pigmentosum group B Benign:1
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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at