ENST00000500358.6:n.680-9612T>C

Variant names:

• chr4-99144933-T-C
• rs3762894
• ENST00000500358.6:n.680-9612T>C

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-9612T>C 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 152,204 control chromosomes in the GnomAD database, including 3,786 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 (3786 hom., cov: 33)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 35 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=-0.93).
• 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.680-9612T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-9612T>C		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-2153A>G		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.676+11128T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29350 AN: 152086 Hom.: 3778 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.193 AC: 29380 AN: 152204 Hom.: 3786 Cov.: 33 AF XY: 0.196 AC XY: 14620 AN XY: 74422

African (AFR) AF: 0.206 AC: 8555 AN: 41524

American (AMR) AF: 0.137 AC: 2098 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3468

East Asian (EAS) AF: 0.733 AC: 3790 AN: 5168

South Asian (SAS) AF: 0.302 AC: 1458 AN: 4822

European-Finnish (FIN) AF: 0.115 AC: 1223 AN: 10606

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

European-Non Finnish (NFE) AF: 0.161 AC: 10954 AN: 68006

Other (OTH) AF: 0.189 AC: 399 AN: 2114

Alfa AF: 0.177 Hom.: 10008

Bravo AF: 0.194

Asia WGS AF: 0.387 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.069
DANN	Benign	0.52
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs3762894; hg19: chr4-100066084;