rs1154405

Variant names:

• chr4-99087599-G-A
• rs1154405
• NM_000671.4:c.12+1090C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99087599-G-A
• chr4-99087599-G-C

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+1090C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,152 control chromosomes in the GnomAD database, including 47,917 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 0.79 (47917 hom., cov: 32)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4	c.12+1090C>T		intron_variant	Intron 1 of 8	ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.12+1090C>T		intron_variant	Intron 1 of 8	1	NM_000671.4	ENSP00000296412.8

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119928 AN: 152034 Hom.: 47865 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.789 AC: 120041 AN: 152152 Hom.: 47917 Cov.: 32 AF XY: 0.797 AC XY: 59260 AN XY: 74382

African (AFR) AF: 0.877 AC: 36432 AN: 41538

American (AMR) AF: 0.798 AC: 12186 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5169 AN: 5184

South Asian (SAS) AF: 0.884 AC: 4267 AN: 4826

European-Finnish (FIN) AF: 0.774 AC: 8171 AN: 10558

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.720 AC: 48955 AN: 67992

Other (OTH) AF: 0.762 AC: 1607 AN: 2110

Alfa AF: 0.739 Hom.: 53475

Bravo AF: 0.795

Asia WGS AF: 0.931 AC: 3236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.21
PhyloP100		-1.5
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: rs1154405; hg19: chr4-100008750;