rs1154409

Positions:

• chr4-99086719-C-A
• chr4-99086719-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000296412.14(ADH5):​c.13-1503G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 151,346 control chromosomes in the GnomAD database, including 2,316 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 0.12 (2316 hom., cov: 30)
• Consequence: ADH5 ENST00000296412.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH5	NM_000671.4	c.13-1503G>T		intron_variant		ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.13-1503G>T		intron_variant		1	NM_000671.4	ENSP00000296412	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18491 AN: 151228 Hom.: 2320 Cov.: 30

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.122 AC: 18477 AN: 151346 Hom.: 2316 Cov.: 30 AF XY: 0.127 AC XY: 9400 AN XY: 73968

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.0803

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0368 Hom.: 24

Bravo AF: 0.120

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1154409; hg19: chr4-100007870;