chr4-99149728-G-A

Variant names:

• chr4-99149728-G-A
• rs17028609
• ENST00000500358.6:n.680-4817G>A

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-4817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,136 control chromosomes in the GnomAD database, including 3,794 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 0.19 (3794 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 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.680-4817G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-4817G>A		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-6948C>T		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.677-7763G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29397 AN: 152018 Hom.: 3786 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.193 AC: 29426 AN: 152136 Hom.: 3794 Cov.: 32 AF XY: 0.197 AC XY: 14627 AN XY: 74360

African (AFR) AF: 0.207 AC: 8606 AN: 41506

American (AMR) AF: 0.137 AC: 2094 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3789 AN: 5166

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4822

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10950 AN: 67992

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.0737 Hom.: 77

Bravo AF: 0.194

Asia WGS AF: 0.386 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.33
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs17028609; hg19: chr4-100070885;