rs11499823

Variant names:

• chr4-99353592-A-G
• rs11499823
• ENST00000865215.1:c.-271T>C

Variant summary

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

The ENST00000865215.1(ADH1C):​c.-271T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 152,168 control chromosomes in the GnomAD database, including 576 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 (576 hom., cov: 32)
• Consequence: ADH1C ENST00000865215.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0989 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.-271T>C		5_prime_UTR	Exon 1 of 10	ENSP00000535274.1
	ADH1C	ENST00000865216.1		c.-268T>C		5_prime_UTR	Exon 1 of 10	ENSP00000535275.1
	ADH1C	ENST00000865217.1		c.-100T>C		5_prime_UTR	Exon 1 of 10	ENSP00000535276.1

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12077 AN: 152050 Hom.: 570 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0794 AC: 12084 AN: 152168 Hom.: 576 Cov.: 32 AF XY: 0.0818 AC XY: 6083 AN XY: 74402

African (AFR) AF: 0.0269 AC: 1119 AN: 41532

American (AMR) AF: 0.0941 AC: 1439 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.0598 AC: 310 AN: 5180

South Asian (SAS) AF: 0.101 AC: 487 AN: 4818

European-Finnish (FIN) AF: 0.142 AC: 1500 AN: 10578

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

European-Non Finnish (NFE) AF: 0.101 AC: 6857 AN: 67986

Other (OTH) AF: 0.0762 AC: 161 AN: 2112

Alfa AF: 0.0884 Hom.: 866

Bravo AF: 0.0740

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.48
PhyloP100		0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11499823; hg19: chr4-100274749;