4-99144933-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.680-9612T>C		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.680-9612T>C		intron_variant	Intron 2 of 9	1
ADH4	ENST00000504581.1	n.170-2153A>G		intron_variant	Intron 1 of 2	3
ENSG00000246090	ENST00000661393.1	n.676+11128T>C		intron_variant	Intron 2 of 9

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

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.189

Alfa AF: 0.166 Hom.: 3369

Bravo AF: 0.194

Asia WGS AF: 0.387 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3762894; hg19: chr4-100066084;