4-99134649-C-T

Variant names:

• chr4-99134649-C-T
• rs10017466
• NM_000670.5:c.582+1817G>A

Variant summary

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

The NM_001306171.2(ADH4):​c.639+1817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,624 control chromosomes in the GnomAD database, including 37,836 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 0.70 (37836 hom., cov: 29)
• Consequence: ADH4 NM_001306171.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345
• Publications: 8 publications found

Genes affected

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]

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 = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306171.2. 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
	ADH4	NM_000670.5	MANE Select	c.582+1817G>A		intron	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.639+1817G>A		intron	N/A	NP_001293100.1
	ADH4	NM_001306172.2		c.639+1817G>A		intron	N/A	NP_001293101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.582+1817G>A		intron	N/A	ENSP00000265512.7
	ENSG00000246090	ENST00000500358.6	TSL:1	n.679+844C>T		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.639+1817G>A		intron	N/A	ENSP00000425416.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106527 AN: 151506 Hom.: 37808 Cov.: 29

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.703 AC: 106600 AN: 151624 Hom.: 37836 Cov.: 29 AF XY: 0.711 AC XY: 52652 AN XY: 74016

African (AFR) AF: 0.670 AC: 27688 AN: 41314

American (AMR) AF: 0.730 AC: 11091 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2317 AN: 3466

East Asian (EAS) AF: 0.998 AC: 5140 AN: 5152

South Asian (SAS) AF: 0.861 AC: 4144 AN: 4812

European-Finnish (FIN) AF: 0.711 AC: 7419 AN: 10436

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46551 AN: 67952

Other (OTH) AF: 0.691 AC: 1452 AN: 2102

Alfa AF: 0.688 Hom.: 14298

Bravo AF: 0.701

Asia WGS AF: 0.894 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.67
PhyloP100		0.34
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: rs10017466; hg19: chr4-100055800;