rs1789920

Variant names:

• chr4-99347699-A-C
• rs1789920
• NM_000669.5:c.120+46T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-99347699-A-C
• chr4-99347699-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.120+46T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,517,206 control chromosomes in the GnomAD database, including 66,912 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 0.23 (4908 hom., cov: 33)
  • Exomes 𝑓: 0.29 (62004 hom.)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1C	NM_000669.5	c.120+46T>G		intron_variant	Intron 2 of 8	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2	n.191+46T>G		intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6	c.120+46T>G		intron_variant	Intron 2 of 8	1	NM_000669.5	ENSP00000426083.1
ADH1C	ENST00000510055.5	c.-1+46T>G		intron_variant	Intron 3 of 6	3		ENSP00000478439.1
ADH1C	ENST00000511397.3	c.19-555T>G		intron_variant	Intron 1 of 4	3		ENSP00000478545.1
ADH1C	ENST00000505942.2	n.189+46T>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35422 AN: 152072 Hom.: 4905 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.255 AC: 51246 AN: 201272 AF XY: 0.259

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.0227

Gnomad FIN exome AF: 0.378

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.292 AC: 398417 AN: 1365016 Hom.: 62004 Cov.: 24 AF XY: 0.290 AC XY: 195914 AN XY: 676538

African (AFR) AF: 0.112 AC: 3332 AN: 29668

American (AMR) AF: 0.184 AC: 6668 AN: 36240

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5210 AN: 23858

East Asian (EAS) AF: 0.0155 AC: 575 AN: 36990

South Asian (SAS) AF: 0.215 AC: 15518 AN: 72086

European-Finnish (FIN) AF: 0.374 AC: 18829 AN: 50392

Middle Eastern (MID) AF: 0.207 AC: 1045 AN: 5058

European-Non Finnish (NFE) AF: 0.315 AC: 332315 AN: 1054532

Other (OTH) AF: 0.266 AC: 14925 AN: 56192

GnomAD4 genome AF: 0.233 AC: 35433 AN: 152190 Hom.: 4908 Cov.: 33 AF XY: 0.231 AC XY: 17185 AN XY: 74396

African (AFR) AF: 0.117 AC: 4855 AN: 41560

American (AMR) AF: 0.198 AC: 3030 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3466

East Asian (EAS) AF: 0.0216 AC: 112 AN: 5188

South Asian (SAS) AF: 0.195 AC: 942 AN: 4826

European-Finnish (FIN) AF: 0.371 AC: 3924 AN: 10568

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21127 AN: 67978

Other (OTH) AF: 0.206 AC: 435 AN: 2112

Alfa AF: 0.241 Hom.: 2436

Bravo AF: 0.213

Asia WGS AF: 0.114 AC: 394 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.3
DANN	Benign	0.65
PhyloP100		0.10

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: rs1789920; hg19: chr4-100268856;