4-99286421-G-T

Variant names:

• chr4-99286421-G-T
• rs1229967
• NM_000667.4:c.259+429C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000667.4(ADH1A):​c.259+429C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 152,174 control chromosomes in the GnomAD database, including 1 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 0.0012 (1 hom., cov: 31)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1A	NM_000667.4	MANE Select	c.259+429C>A		intron	N/A	NP_000658.1	P07327
	LOC100507053	NR_037884.1		n.3790-374G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1A	ENST00000209668.3	TSL:1 MANE Select	c.259+429C>A		intron	N/A	ENSP00000209668.2	P07327
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3790-374G>T		intron	N/A
	ADH1A	ENST00000503461.5	TSL:1	n.348+429C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152056 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152174 Hom.: 1 Cov.: 31 AF XY: 0.00126 AC XY: 94 AN XY: 74386

African (AFR) AF: 0.00424 AC: 176 AN: 41538

American (AMR) AF: 0.000196 AC: 3 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 2074

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		0.052

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: rs1229967; hg19: chr4-100207578;