rs1693427

Variant names:

• chr4-99345670-T-C
• rs1693427
• NM_000669.5:c.260-404A>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.260-404A>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 152,128 control chromosomes in the GnomAD database, including 8,839 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 (8839 hom., cov: 33)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 4 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=-0.94).
• 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.260-404A>G		intron_variant	Intron 3 of 8	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2	n.331-404A>G		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6	c.260-404A>G		intron_variant	Intron 3 of 8	1	NM_000669.5	ENSP00000426083.1
ADH1C	ENST00000510055.5	c.140-404A>G		intron_variant	Intron 4 of 6	3		ENSP00000478439.1
ADH1C	ENST00000511397.3	c.158-404A>G		intron_variant	Intron 2 of 4	3		ENSP00000478545.1
ADH1C	ENST00000505942.2	n.329-450A>G		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47444 AN: 152010 Hom.: 8833 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.247

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: 47465 AN: 152128 Hom.: 8839 Cov.: 33 AF XY: 0.313 AC XY: 23242 AN XY: 74370

African (AFR) AF: 0.144 AC: 5965 AN: 41538

American (AMR) AF: 0.292 AC: 4471 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3472

East Asian (EAS) AF: 0.0808 AC: 419 AN: 5184

South Asian (SAS) AF: 0.296 AC: 1427 AN: 4826

European-Finnish (FIN) AF: 0.512 AC: 5400 AN: 10550

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27968 AN: 67956

Other (OTH) AF: 0.281 AC: 592 AN: 2104

Alfa AF: 0.364 Hom.: 1475

Bravo AF: 0.287

Asia WGS AF: 0.217 AC: 752 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.27
PhyloP100		-2.0

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: rs1693427; hg19: chr4-100266827; COSMIC: COSV72463519;