ENST00000500358.6:n.3714+15C>A

Variant names:

• chr4-99157594-C-A
• rs7678890
• ENST00000500358.6:n.3714+15C>A

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.3714+15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,216 control chromosomes in the GnomAD database, including 60,679 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 0.89 (60679 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.3714+15C>A		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.3714+15C>A		intron_variant	Intron 3 of 9	1
ADH4	ENST00000504581.1	n.169+30G>T		intron_variant	Intron 1 of 2	3
ENSG00000246090	ENST00000661393.1	n.765+15C>A		intron_variant	Intron 3 of 9

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135177 AN: 152098 Hom.: 60652 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.916

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.889 AC: 135253 AN: 152216 Hom.: 60679 Cov.: 32 AF XY: 0.890 AC XY: 66230 AN XY: 74404

African (AFR) AF: 0.750 AC: 31131 AN: 41498

American (AMR) AF: 0.926 AC: 14153 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3342 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5183 AN: 5186

South Asian (SAS) AF: 0.969 AC: 4677 AN: 4828

European-Finnish (FIN) AF: 0.909 AC: 9638 AN: 10598

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64015 AN: 68024

Other (OTH) AF: 0.917 AC: 1940 AN: 2116

Alfa AF: 0.887 Hom.: 3259

Bravo AF: 0.881

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.44
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs7678890; hg19: chr4-100078751;