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rs2018417

chr4-99313983-C-Achr4-99313983-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000668.6(ADH1B):c.666G>T(p.Ala222=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,613,964 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 75 hom., cov: 32)
Exomes 𝑓: 0.031 ( 833 hom. )

Consequence

ADH1B
NM_000668.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.70
Variant links:
Genes affected
ADH1B (HGNC:250): (alcohol dehydrogenase 1B (class I), beta polypeptide) The protein encoded by this gene 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. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-99313983-C-A is Benign according to our data. Variant chr4-99313983-C-A is described in ClinVar as [Benign]. Clinvar id is 769290.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.7 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0292 (4451/152230) while in subpopulation AFR AF= 0.035 (1454/41538). AF 95% confidence interval is 0.0335. There are 75 homozygotes in gnomad4. There are 2122 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 75 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADH1BNM_000668.6 linkuse as main transcriptc.666G>T p.Ala222= synonymous_variant 6/9 ENST00000305046.13
ADH1BNM_001286650.2 linkuse as main transcriptc.546G>T p.Ala182= synonymous_variant 7/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADH1BENST00000305046.13 linkuse as main transcriptc.666G>T p.Ala222= synonymous_variant 6/91 NM_000668.6 P1P00325-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0292
AC:
4442
AN:
152112
Hom.:
75
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0349
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.0146
Gnomad ASJ
AF:
0.0115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0135
Gnomad FIN
AF:
0.0345
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0330
Gnomad OTH
AF:
0.0244
GnomAD3 exomes
AF:
0.0222
AC:
5555
AN:
250462
Hom.:
105
AF XY:
0.0221
AC XY:
2998
AN XY:
135364
show subpopulations
Gnomad AFR exome
AF:
0.0322
Gnomad AMR exome
AF:
0.00825
Gnomad ASJ exome
AF:
0.0113
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0157
Gnomad FIN exome
AF:
0.0338
Gnomad NFE exome
AF:
0.0293
Gnomad OTH exome
AF:
0.0193
GnomAD4 exome
AF:
0.0312
AC:
45613
AN:
1461734
Hom.:
833
Cov.:
33
AF XY:
0.0305
AC XY:
22203
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.0352
Gnomad4 AMR exome
AF:
0.00915
Gnomad4 ASJ exome
AF:
0.0146
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0182
Gnomad4 FIN exome
AF:
0.0359
Gnomad4 NFE exome
AF:
0.0346
Gnomad4 OTH exome
AF:
0.0246
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0292
AC:
4451
AN:
152230
Hom.:
75
Cov.:
32
AF XY:
0.0285
AC XY:
2122
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0350
Gnomad4 AMR
AF:
0.0146
Gnomad4 ASJ
AF:
0.0115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0133
Gnomad4 FIN
AF:
0.0345
Gnomad4 NFE
AF:
0.0330
Gnomad4 OTH
AF:
0.0241
Alfa
AF:
0.0232
Hom.:
20
Bravo
AF:
0.0279

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
0.61
Dann
Benign
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2018417; hg19: chr4-100235140; COSMIC: COSV59296113; COSMIC: COSV59296113; API