ENST00000500358.6:n.680-5850G>C

Variant names:

• chr4-99148695-G-C
• rs7434491
• ENST00000500358.6:n.680-5850G>C

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-5850G>C 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 152,094 control chromosomes in the GnomAD database, including 3,879 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 (3879 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 2 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=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.680-5850G>C		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.680-5850G>C		intron_variant	Intron 2 of 9	1
ADH4	ENST00000504581.1	n.170-5915C>G		intron_variant	Intron 1 of 2	3
ENSG00000246090	ENST00000661393.1	n.677-8796G>C		intron_variant	Intron 2 of 9

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31009 AN: 151976 Hom.: 3882 Cov.: 32

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.204 AC: 31008 AN: 152094 Hom.: 3879 Cov.: 32 AF XY: 0.197 AC XY: 14630 AN XY: 74328

African (AFR) AF: 0.0917 AC: 3807 AN: 41514

American (AMR) AF: 0.206 AC: 3153 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5176

South Asian (SAS) AF: 0.116 AC: 561 AN: 4830

European-Finnish (FIN) AF: 0.232 AC: 2447 AN: 10554

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19129 AN: 67964

Other (OTH) AF: 0.231 AC: 488 AN: 2110

Alfa AF: 0.138 Hom.: 286

Bravo AF: 0.197

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs7434491; hg19: chr4-100069847;