4-99353000-G-C

Variant names:

• chr4-99353000-G-C
• rs4147541
• ENST00000865215.1:c.-60-265C>G

Variant summary

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

The ENST00000865215.1(ADH1C):​c.-60-265C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 238,322 control chromosomes in the GnomAD database, including 15,861 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 0.34 (9951 hom., cov: 32)
  • Exomes 𝑓: 0.33 (5910 hom.)
• Consequence: ADH1C ENST00000865215.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000865215.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1C	ENST00000865215.1		c.-60-265C>G		intron	N/A	ENSP00000535274.1
	ADH1C	ENST00000865216.1		c.-57-268C>G		intron	N/A	ENSP00000535275.1
	ADH1C	ENST00000865217.1		c.-57-268C>G		intron	N/A	ENSP00000535276.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51047 AN: 151806 Hom.: 9951 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.331 AC: 28557 AN: 86400 Hom.: 5910 Cov.: 0 AF XY: 0.341 AC XY: 15505 AN XY: 45524

African (AFR) AF: 0.471 AC: 1352 AN: 2868

American (AMR) AF: 0.195 AC: 824 AN: 4236

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 670 AN: 2962

East Asian (EAS) AF: 0.842 AC: 5193 AN: 6168

South Asian (SAS) AF: 0.530 AC: 3301 AN: 6230

European-Finnish (FIN) AF: 0.216 AC: 704 AN: 3258

Middle Eastern (MID) AF: 0.286 AC: 116 AN: 406

European-Non Finnish (NFE) AF: 0.270 AC: 14860 AN: 54988

Other (OTH) AF: 0.291 AC: 1537 AN: 5284

GnomAD4 genome AF: 0.336 AC: 51075 AN: 151922 Hom.: 9951 Cov.: 32 AF XY: 0.340 AC XY: 25246 AN XY: 74254

African (AFR) AF: 0.468 AC: 19363 AN: 41402

American (AMR) AF: 0.222 AC: 3386 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3466

East Asian (EAS) AF: 0.754 AC: 3906 AN: 5178

South Asian (SAS) AF: 0.548 AC: 2639 AN: 4814

European-Finnish (FIN) AF: 0.191 AC: 2007 AN: 10534

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18035 AN: 67962

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.290 Hom.: 4247

Bravo AF: 0.337

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.39
PhyloP100		-0.18
PromoterAI		0.16	Neutral

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: rs4147541; hg19: chr4-100274157;