4-99342788-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000669.5(ADH1C):​c.828+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,610,326 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 14 hom. )

Consequence

ADH1C
NM_000669.5 splice_region, intron

Scores

2
Splicing: ADA: 0.00001002
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.185
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 4-99342788-A-T is Benign according to our data. Variant chr4-99342788-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654964.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADH1CNM_000669.5 linkuse as main transcriptc.828+7T>A splice_region_variant, intron_variant ENST00000515683.6 NP_000660.1
ADH1CNR_133005.2 linkuse as main transcriptn.855+51T>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADH1CENST00000515683.6 linkuse as main transcriptc.828+7T>A splice_region_variant, intron_variant 1 NM_000669.5 ENSP00000426083 P1

Frequencies

GnomAD3 genomes
AF:
0.00285
AC:
434
AN:
152242
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000530
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
Gnomad ASJ
AF:
0.00749
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00500
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00169
AC:
424
AN:
250476
Hom.:
2
AF XY:
0.00172
AC XY:
233
AN XY:
135416
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00165
Gnomad ASJ exome
AF:
0.00339
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000915
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00251
Gnomad OTH exome
AF:
0.00262
GnomAD4 exome
AF:
0.00282
AC:
4111
AN:
1457966
Hom.:
14
Cov.:
70
AF XY:
0.00273
AC XY:
1983
AN XY:
725396
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.00453
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00110
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.00327
Gnomad4 OTH exome
AF:
0.00269
GnomAD4 genome
AF:
0.00285
AC:
434
AN:
152360
Hom.:
2
Cov.:
33
AF XY:
0.00250
AC XY:
186
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.000529
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00749
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00498
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.00441
Hom.:
0
Bravo
AF:
0.00278

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 submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022ADH1C: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.45
DANN
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000010
dbscSNV1_RF
Benign
0.0
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: rs6413446; hg19: chr4-100263945; API