4-99087853-A-T

Variant names:

• chr4-99087853-A-T
• rs1154404
• NM_000671.4:c.12+836T>A

Variant summary

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

The NM_000671.4(ADH5):​c.12+836T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,132 control chromosomes in the GnomAD database, including 10,336 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 0.34 (10336 hom., cov: 33)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 5 publications found

Genes affected

ADH5 (HGNC:253): (alcohol dehydrogenase 5 (class III), chi polypeptide) This gene encodes a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The encoded protein forms a homodimer. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. The human genome contains several non-transcribed pseudogenes related to this gene. [provided by RefSeq, Oct 2008]

ADH5 Gene-Disease associations (from GenCC):

• AMED syndrome, digenic

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000246090 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000671.4. 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
	ADH5	NM_000671.4	MANE Select	c.12+836T>A		intron	N/A	NP_000662.3	P11766

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	ENST00000296412.14	TSL:1 MANE Select	c.12+836T>A		intron	N/A	ENSP00000296412.8	P11766
	ADH5	ENST00000885760.1		c.12+836T>A		intron	N/A	ENSP00000555819.1
	ADH5	ENST00000929295.1		c.12+836T>A		intron	N/A	ENSP00000599354.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51430 AN: 152014 Hom.: 10331 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.338 AC: 51435 AN: 152132 Hom.: 10336 Cov.: 33 AF XY: 0.341 AC XY: 25377 AN XY: 74366

African (AFR) AF: 0.134 AC: 5563 AN: 41500

American (AMR) AF: 0.329 AC: 5022 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3470

East Asian (EAS) AF: 0.129 AC: 670 AN: 5180

South Asian (SAS) AF: 0.512 AC: 2471 AN: 4828

European-Finnish (FIN) AF: 0.453 AC: 4786 AN: 10572

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30331 AN: 67982

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.259 Hom.: 726

Bravo AF: 0.313

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		0.030
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: rs1154404; hg19: chr4-100009004;