rs1391088

Variant names:

• chr4-99337067-A-C
• rs1391088
• NM_000669.5:c.1104-291T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-99337067-A-C
• chr4-99337067-A-G
• chr4-99337067-A-T

Variant summary

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

The NM_000669.5(ADH1C):​c.1104-291T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 152,264 control chromosomes in the GnomAD database, including 66,315 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 0.93 (66315 hom., cov: 32)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1C	NM_000669.5	c.1104-291T>G		intron_variant	Intron 8 of 8	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2	n.1131-291T>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6	c.1104-291T>G		intron_variant	Intron 8 of 8	1	NM_000669.5	ENSP00000426083.1

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141954 AN: 152148 Hom.: 66269 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.933 AC: 142059 AN: 152264 Hom.: 66315 Cov.: 32 AF XY: 0.935 AC XY: 69614 AN XY: 74436

African (AFR) AF: 0.915 AC: 38009 AN: 41542

American (AMR) AF: 0.959 AC: 14650 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5186 AN: 5190

South Asian (SAS) AF: 0.943 AC: 4545 AN: 4820

European-Finnish (FIN) AF: 0.962 AC: 10214 AN: 10612

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63235 AN: 68030

Other (OTH) AF: 0.937 AC: 1976 AN: 2108

Alfa AF: 0.933 Hom.: 6085

Bravo AF: 0.933

Asia WGS AF: 0.975 AC: 3393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1391088; hg19: chr4-100258224;