rs1154414

chr4-99078985-T-C

Variant summary

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

The NM_000671.4(ADH5):c.345-2062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,264 control chromosomes in the GnomAD database, including 2,553 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 0.13 (2553 hom., cov: 33)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH5	NM_000671.4	c.345-2062A>G		intron_variant		ENST00000296412.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH5	ENST00000296412.14	c.345-2062A>G		intron_variant		1	NM_000671.4	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20184 AN: 152148 Hom.: 2558 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.132 AC: 20166 AN: 152264 Hom.: 2553 Cov.: 33 AF XY: 0.137 AC XY: 10213 AN XY: 74452

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.137

Alfa AF: 0.131 Hom.: 198

Bravo AF: 0.127

Asia WGS AF: 0.359 AC: 1244 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	8.4
Dann	Benign	0.75

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: rs1154414; hg19: chr4-100000136;