rs283416

Variant names:

• chr4-99350199-G-A
• rs283416
• NM_000669.5:c.19-2353C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99350199-G-A
• chr4-99350199-G-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.19-2353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 152,174 control chromosomes in the GnomAD database, including 378 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 0.067 (378 hom., cov: 32)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000669.5. 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
	ADH1C	NM_000669.5	MANE Select	c.19-2353C>T		intron	N/A	NP_000660.1
	ADH1C	NR_133005.2		n.90-2353C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1C	ENST00000515683.6	TSL:1 MANE Select	c.19-2353C>T		intron	N/A	ENSP00000426083.1
	ADH1C	ENST00000865215.1		c.19-2353C>T		intron	N/A	ENSP00000535274.1
	ADH1C	ENST00000865216.1		c.19-2353C>T		intron	N/A	ENSP00000535275.1

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10219 AN: 152056 Hom.: 376 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0865

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0751

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

GnomAD4 genome AF: 0.0672 AC: 10231 AN: 152174 Hom.: 378 Cov.: 32 AF XY: 0.0655 AC XY: 4871 AN XY: 74386

African (AFR) AF: 0.0652 AC: 2706 AN: 41506

American (AMR) AF: 0.0632 AC: 967 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4816

European-Finnish (FIN) AF: 0.100 AC: 1060 AN: 10586

Middle Eastern (MID) AF: 0.0897 AC: 26 AN: 290

European-Non Finnish (NFE) AF: 0.0693 AC: 4712 AN: 68004

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0681 Hom.: 701

Bravo AF: 0.0670

Asia WGS AF: 0.0200 AC: 71 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	6.2
DANN	Benign	0.57
PhyloP100		-0.12

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: rs283416; hg19: chr4-100271356;