rs2226896

Variant names:

• chr4-99146186-A-G
• rs2226896
• ENST00000500358.6:n.680-8359A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-99146186-A-G
• chr4-99146186-A-T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-8359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,084 control chromosomes in the GnomAD database, including 942 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 0.089 (942 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 6 publications found

Genes affected

ENSG00000246090 (HGNC:):

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi 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 II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500358.6. 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
	LOC100507053	NR_037884.1		n.680-8359A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-8359A>G		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-3406T>C		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.677-11305A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13578 AN: 151964 Hom.: 938 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0873

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

GnomAD4 genome AF: 0.0894 AC: 13594 AN: 152084 Hom.: 942 Cov.: 32 AF XY: 0.0945 AC XY: 7024 AN XY: 74338

African (AFR) AF: 0.0447 AC: 1854 AN: 41496

American (AMR) AF: 0.233 AC: 3554 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 280 AN: 3472

East Asian (EAS) AF: 0.140 AC: 725 AN: 5182

South Asian (SAS) AF: 0.0608 AC: 293 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10548

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5273 AN: 67996

Other (OTH) AF: 0.0878 AC: 185 AN: 2108

Alfa AF: 0.0887 Hom.: 1301

Bravo AF: 0.100

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.7
DANN	Benign	0.67
PhyloP100		-0.17

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2226896;

hg19: chr4-100067337;