rs1984362

Variant names:

• chr4-99149816-G-A
• rs1984362
• ENST00000500358.6:n.680-4729G>A

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-4729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,120 control chromosomes in the GnomAD database, including 3,882 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 0.20 (3882 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 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.680-4729G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-4729G>A		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-7036C>T		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.677-7675G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31017 AN: 152002 Hom.: 3885 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.204 AC: 31016 AN: 152120 Hom.: 3882 Cov.: 32 AF XY: 0.197 AC XY: 14655 AN XY: 74386

African (AFR) AF: 0.0918 AC: 3808 AN: 41502

American (AMR) AF: 0.206 AC: 3148 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.116 AC: 561 AN: 4824

European-Finnish (FIN) AF: 0.233 AC: 2460 AN: 10580

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19128 AN: 67978

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.237 Hom.: 634

Bravo AF: 0.197

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		0.36

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1984362;

hg19: chr4-100070973;