chr4-99138581-T-A

Variant names:

• chr4-99138581-T-A
• rs7694646
• NM_000670.5:c.350+480A>T

Variant summary

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

The NM_000670.5(ADH4):​c.350+480A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,188 control chromosomes in the GnomAD database, including 4,039 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 (4039 hom., cov: 33)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 7 publications found

Genes affected

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]

ENSG00000246090 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000670.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	NM_000670.5	MANE Select	c.350+480A>T		intron	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.407+480A>T		intron	N/A	NP_001293100.1
	ADH4	NM_001306172.2		c.407+480A>T		intron	N/A	NP_001293101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.350+480A>T		intron	N/A	ENSP00000265512.7
	ENSG00000246090	ENST00000500358.6	TSL:1	n.679+4776T>A		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.407+480A>T		intron	N/A	ENSP00000425416.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31976 AN: 152070 Hom.: 4042 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.210 AC: 31977 AN: 152188 Hom.: 4039 Cov.: 33 AF XY: 0.203 AC XY: 15073 AN XY: 74412

African (AFR) AF: 0.108 AC: 4487 AN: 41550

American (AMR) AF: 0.208 AC: 3170 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5192

South Asian (SAS) AF: 0.116 AC: 561 AN: 4828

European-Finnish (FIN) AF: 0.233 AC: 2474 AN: 10596

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

European-Non Finnish (NFE) AF: 0.285 AC: 19366 AN: 67964

Other (OTH) AF: 0.237 AC: 500 AN: 2110

Alfa AF: 0.248 Hom.: 663

Bravo AF: 0.203

Asia WGS AF: 0.0680 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.7
DANN	Benign	0.81
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7694646; hg19: chr4-100059732;