rs1800760

Variant names:

• chr4-99144475-A-T
• rs1800760
• ENST00000500358.6:n.680-10070A>T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-10070A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,080 control chromosomes in the GnomAD database, including 10,416 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 0.34 (10416 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100507053	NR_037884.1		n.680-10070A>T		intron	N/A
	ADH4	NM_000670.5	MANE Select	c.-253T>A		upstream_gene	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.-344T>A		upstream_gene	N/A	NP_001293100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-10070A>T		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-1695T>A		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.676+10670A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51596 AN: 151962 Hom.: 10413 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.339 AC: 51602 AN: 152080 Hom.: 10416 Cov.: 32 AF XY: 0.342 AC XY: 25445 AN XY: 74334

African (AFR) AF: 0.134 AC: 5581 AN: 41516

American (AMR) AF: 0.330 AC: 5046 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3470

East Asian (EAS) AF: 0.123 AC: 637 AN: 5180

South Asian (SAS) AF: 0.498 AC: 2402 AN: 4826

European-Finnish (FIN) AF: 0.463 AC: 4872 AN: 10518

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30460 AN: 67982

Other (OTH) AF: 0.355 AC: 750 AN: 2112

Alfa AF: 0.392 Hom.: 1596

Bravo AF: 0.315

Asia WGS AF: 0.363 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.50
DANN	Benign	0.73
PhyloP100		-2.5
PromoterAI		-0.021	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1800760; hg19: chr4-100065626;