4-99134711-A-G

Variant names:

• chr4-99134711-A-G
• rs4148887
• NM_000670.5:c.582+1755T>C

Variant summary

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

The NM_000670.5(ADH4):​c.582+1755T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,852 control chromosomes in the GnomAD database, including 2,425 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 0.12 (2425 hom., cov: 30)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 5 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 = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000670.5. 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
	ADH4	NM_000670.5	MANE Select	c.582+1755T>C		intron	N/A	NP_000661.2	P08319-1
	ADH4	NM_001306171.2		c.639+1755T>C		intron	N/A	NP_001293100.1	P08319-2
	ADH4	NM_001306172.2		c.639+1755T>C		intron	N/A	NP_001293101.1	P08319-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.582+1755T>C		intron	N/A	ENSP00000265512.7	P08319-1
	ENSG00000246090	ENST00000500358.6	TSL:1	n.679+906A>G		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.639+1755T>C		intron	N/A	ENSP00000425416.1	P08319-2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18789 AN: 151734 Hom.: 2427 Cov.: 30

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.124 AC: 18780 AN: 151852 Hom.: 2425 Cov.: 30 AF XY: 0.129 AC XY: 9548 AN XY: 74150

African (AFR) AF: 0.0325 AC: 1345 AN: 41418

American (AMR) AF: 0.106 AC: 1613 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3772 AN: 5144

South Asian (SAS) AF: 0.289 AC: 1391 AN: 4806

European-Finnish (FIN) AF: 0.0795 AC: 837 AN: 10530

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8674 AN: 67958

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.131 Hom.: 2464

Bravo AF: 0.120

Asia WGS AF: 0.367 AC: 1274 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	4.0
DANN	Benign	0.65
PhyloP100		-0.14
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: rs4148887; hg19: chr4-100055862;