4-99342789-T-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_000669.5(ADH1C):c.828+6A>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,610,308 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0024 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 9 hom. )
Consequence
ADH1C
NM_000669.5 splice_donor_region, intron
NM_000669.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00001616
2
Clinical Significance
Conservation
PhyloP100: 2.15
Genes affected
ADH1C (HGNC:251): (alcohol dehydrogenase 1C (class I), gamma polypeptide) This gene encodes class I alcohol dehydrogenase, gamma subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class I alcohol dehydrogenase, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation to acetaldehyde, thus playing a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. An association between ADH1C polymorphism and alcohol dependence has not been established. [provided by RefSeq, Sep 2019]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 4-99342789-T-A is Benign according to our data. Variant chr4-99342789-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654965.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADH1C | NM_000669.5 | c.828+6A>T | splice_donor_region_variant, intron_variant | ENST00000515683.6 | |||
ADH1C | NR_133005.2 | n.855+50A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADH1C | ENST00000515683.6 | c.828+6A>T | splice_donor_region_variant, intron_variant | 1 | NM_000669.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00237 AC: 361AN: 152204Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00129 AC: 324AN: 250496Hom.: 1 AF XY: 0.00134 AC XY: 182AN XY: 135418
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GnomAD4 exome AF: 0.00218 AC: 3182AN: 1457986Hom.: 9 Cov.: 71 AF XY: 0.00215 AC XY: 1556AN XY: 725402
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GnomAD4 genome ? AF: 0.00238 AC: 362AN: 152322Hom.: 1 Cov.: 33 AF XY: 0.00208 AC XY: 155AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | ADH1C: BP4 - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at