rs7689753

Variant names:

• chr4-99134424-A-G
• rs7689753
• NM_000670.5:c.582+2042T>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+2042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,956 control chromosomes in the GnomAD database, including 4,031 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 0.21 (4031 hom., cov: 31)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH4	NM_000670.5	c.582+2042T>C		intron_variant	Intron 5 of 8	ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.639+2042T>C		intron_variant	Intron 6 of 9		NP_001293100.1
ADH4	NM_001306172.2	c.639+2042T>C		intron_variant	Intron 6 of 9		NP_001293101.1
LOC100507053	NR_037884.1	n.679+619A>G		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.582+2042T>C		intron_variant	Intron 5 of 8	1	NM_000670.5	ENSP00000265512.7

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31948 AN: 151838 Hom.: 4034 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.210 AC: 31949 AN: 151956 Hom.: 4031 Cov.: 31 AF XY: 0.203 AC XY: 15042 AN XY: 74272

African (AFR) AF: 0.109 AC: 4518 AN: 41488

American (AMR) AF: 0.208 AC: 3168 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.116 AC: 557 AN: 4814

European-Finnish (FIN) AF: 0.232 AC: 2437 AN: 10506

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19349 AN: 67930

Other (OTH) AF: 0.237 AC: 499 AN: 2102

Alfa AF: 0.243 Hom.: 665

Bravo AF: 0.204

Asia WGS AF: 0.0670 AC: 234 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.090
DANN	Benign	0.45
PhyloP100		-1.3
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: rs7689753; hg19: chr4-100055575;