4-99344907-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000669.5(ADH1C):c.522C>T(p.Gly174Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,614,160 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0039 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0063 ( 43 hom. )
Consequence
ADH1C
NM_000669.5 synonymous
NM_000669.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.931
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 Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 4-99344907-G-A is Benign according to our data. Variant chr4-99344907-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 776589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.931 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 43 AR gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADH1C | ENST00000515683.6 | c.522C>T | p.Gly174Gly | synonymous_variant | 5/9 | 1 | NM_000669.5 | ENSP00000426083.1 | ||
ADH1C | ENST00000510055.5 | c.402C>T | p.Gly134Gly | synonymous_variant | 6/7 | 3 | ENSP00000478439.1 | |||
ADH1C | ENST00000511397.3 | c.420C>T | p.Gly140Gly | synonymous_variant | 4/5 | 3 | ENSP00000478545.1 | |||
ADH1C | ENST00000505942.2 | n.545C>T | non_coding_transcript_exon_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00386 AC: 587AN: 152160Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00462 AC: 1163AN: 251464Hom.: 7 AF XY: 0.00501 AC XY: 681AN XY: 135908
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GnomAD4 exome AF: 0.00633 AC: 9261AN: 1461882Hom.: 43 Cov.: 31 AF XY: 0.00631 AC XY: 4591AN XY: 727240
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GnomAD4 genome AF: 0.00385 AC: 587AN: 152278Hom.: 1 Cov.: 33 AF XY: 0.00393 AC XY: 293AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 03, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | ADH1C: BP4 - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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