rs4140388

Variant names:

• chr4-99144583-G-C
• rs4140388
• ENST00000500358.6:n.680-9962G>C

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-9962G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,048 control chromosomes in the GnomAD database, including 24,395 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 0.56 (24395 hom., cov: 33)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 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.680-9962G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-9962G>C		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-1803C>G		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.676+10778G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85098 AN: 151930 Hom.: 24368 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.560 AC: 85178 AN: 152048 Hom.: 24395 Cov.: 33 AF XY: 0.564 AC XY: 41904 AN XY: 74308

African (AFR) AF: 0.631 AC: 26177 AN: 41500

American (AMR) AF: 0.612 AC: 9333 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1362 AN: 5160

South Asian (SAS) AF: 0.561 AC: 2698 AN: 4812

European-Finnish (FIN) AF: 0.596 AC: 6296 AN: 10558

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35920 AN: 67970

Other (OTH) AF: 0.546 AC: 1154 AN: 2114

Alfa AF: 0.545 Hom.: 2831

Bravo AF: 0.564

Asia WGS AF: 0.522 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.36
PhyloP100		-0.44
PromoterAI		-0.013	Neutral

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: rs4140388;

hg19: chr4-100065734;