4-99280582-G-C

Variant names:

• chr4-99280582-G-C
• rs975833
• NM_000667.4:c.829-303C>G

Variant summary

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

The NM_000667.4(ADH1A):​c.829-303C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,048 control chromosomes in the GnomAD database, including 6,342 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 0.27 (6342 hom., cov: 32)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 25 publications found

Genes affected

ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]

ENSG00000246090 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000667.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1A	NM_000667.4	MANE Select	c.829-303C>G		intron	N/A	NP_000658.1
	LOC100507053	NR_037884.1		n.3790-6213G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1A	ENST00000209668.3	TSL:1 MANE Select	c.829-303C>G		intron	N/A	ENSP00000209668.2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3790-6213G>C		intron	N/A
	ENSG00000246090	ENST00000506160.1	TSL:4	n.465-600G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40884 AN: 151930 Hom.: 6349 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.269 AC: 40873 AN: 152048 Hom.: 6342 Cov.: 32 AF XY: 0.270 AC XY: 20082 AN XY: 74332

African (AFR) AF: 0.280 AC: 11609 AN: 41466

American (AMR) AF: 0.201 AC: 3063 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3470

East Asian (EAS) AF: 0.794 AC: 4112 AN: 5176

South Asian (SAS) AF: 0.441 AC: 2127 AN: 4824

European-Finnish (FIN) AF: 0.161 AC: 1706 AN: 10572

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16498 AN: 67952

Other (OTH) AF: 0.261 AC: 550 AN: 2108

Alfa AF: 0.141 Hom.: 231

Bravo AF: 0.270

Asia WGS AF: 0.471 AC: 1635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.72
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs975833; hg19: chr4-100201739;