rs17586023

Variant names:

• chr4-99351793-A-G
• rs17586023
• NM_000669.5:c.18+865T>C

Variant summary

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

The NM_000669.5(ADH1C):​c.18+865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 152,300 control chromosomes in the GnomAD database, including 575 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 0.079 (575 hom., cov: 33)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1C	NM_000669.5	c.18+865T>C		intron_variant	Intron 1 of 8	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2	n.89+865T>C		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6	c.18+865T>C		intron_variant	Intron 1 of 8	1	NM_000669.5	ENSP00000426083.1
ADH1C	ENST00000510055.5	c.-222-661T>C		intron_variant	Intron 1 of 6	3		ENSP00000478439.1
ADH1C	ENST00000511397.3	c.18+865T>C		intron_variant	Intron 1 of 4	3		ENSP00000478545.1
ADH1C	ENST00000505942.2	n.87+865T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12086 AN: 152182 Hom.: 569 Cov.: 33

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0794 AC: 12093 AN: 152300 Hom.: 575 Cov.: 33 AF XY: 0.0817 AC XY: 6085 AN XY: 74470

African (AFR) AF: 0.0271 AC: 1128 AN: 41576

American (AMR) AF: 0.0940 AC: 1439 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3472

East Asian (EAS) AF: 0.0596 AC: 309 AN: 5188

South Asian (SAS) AF: 0.101 AC: 488 AN: 4828

European-Finnish (FIN) AF: 0.141 AC: 1499 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6856 AN: 68012

Other (OTH) AF: 0.0762 AC: 161 AN: 2114

Alfa AF: 0.0915 Hom.: 102

Bravo AF: 0.0740

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		0.075

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: rs17586023; hg19: chr4-100272950;