rs4699718

Variant names:

• chr4-99146639-G-A
• rs4699718
• ENST00000500358.6:n.680-7906G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-99146639-G-A
• chr4-99146639-G-T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-7906G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,982 control chromosomes in the GnomAD database, including 3,972 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 0.21 (3972 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• 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=-0.97).
• 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.680-7906G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-7906G>A		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-3859C>T		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.677-10852G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31762 AN: 151864 Hom.: 3973 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.209 AC: 31768 AN: 151982 Hom.: 3972 Cov.: 32 AF XY: 0.202 AC XY: 14979 AN XY: 74258

African (AFR) AF: 0.109 AC: 4527 AN: 41450

American (AMR) AF: 0.208 AC: 3170 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3464

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

South Asian (SAS) AF: 0.116 AC: 560 AN: 4814

European-Finnish (FIN) AF: 0.232 AC: 2447 AN: 10548

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

European-Non Finnish (NFE) AF: 0.282 AC: 19143 AN: 67942

Other (OTH) AF: 0.236 AC: 497 AN: 2110

Alfa AF: 0.232 Hom.: 600

Bravo AF: 0.202

Asia WGS AF: 0.0680 AC: 237 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.11
PhyloP100		-0.10

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: rs4699718;

hg19: chr4-100067791;