chr4-99286421-G-C

Variant names:

• chr4-99286421-G-C
• rs1229967
• NM_000667.4:c.259+429C>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.259+429C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,116 control chromosomes in the GnomAD database, including 51,031 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 0.82 (51031 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 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.259+429C>G		intron	N/A	NP_000658.1
	LOC100507053	NR_037884.1		n.3790-374G>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.259+429C>G		intron	N/A	ENSP00000209668.2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3790-374G>C		intron	N/A
	ADH1A	ENST00000503461.5	TSL:1	n.348+429C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124092 AN: 151998 Hom.: 50978 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.816 AC: 124200 AN: 152116 Hom.: 51031 Cov.: 31 AF XY: 0.811 AC XY: 60335 AN XY: 74356

African (AFR) AF: 0.906 AC: 37628 AN: 41530

American (AMR) AF: 0.808 AC: 12342 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2927 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4690 AN: 5146

South Asian (SAS) AF: 0.701 AC: 3371 AN: 4806

European-Finnish (FIN) AF: 0.733 AC: 7768 AN: 10594

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.776 AC: 52769 AN: 67972

Other (OTH) AF: 0.824 AC: 1742 AN: 2114

Alfa AF: 0.723 Hom.: 2074

Bravo AF: 0.832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.31
PhyloP100		0.052
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: rs1229967; hg19: chr4-100207578;