rs1789898

Variant names:

• chr4-99337179-A-C
• rs1789898
• NM_000669.5:c.1104-403T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-99337179-A-C
• chr4-99337179-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000669.5(ADH1C):​c.1104-403T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,994 control chromosomes in the GnomAD database, including 8,849 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8849 hom., cov: 31)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1C	NM_000669.5	c.1104-403T>G		intron_variant	Intron 8 of 8	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2	n.1131-403T>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6	c.1104-403T>G		intron_variant	Intron 8 of 8	1	NM_000669.5	ENSP00000426083.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47445 AN: 151876 Hom.: 8842 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47466 AN: 151994 Hom.: 8849 Cov.: 31 AF XY: 0.313 AC XY: 23231 AN XY: 74268

African (AFR) AF: 0.144 AC: 5966 AN: 41474

American (AMR) AF: 0.293 AC: 4472 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 941 AN: 3462

East Asian (EAS) AF: 0.0814 AC: 422 AN: 5186

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4814

European-Finnish (FIN) AF: 0.512 AC: 5398 AN: 10534

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 27974 AN: 67956

Other (OTH) AF: 0.282 AC: 594 AN: 2108

Alfa AF: 0.284 Hom.: 1227

Bravo AF: 0.287

Asia WGS AF: 0.219 AC: 759 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.80

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

Other links and lift over

dbSNP: rs1789898; hg19: chr4-100258336;