rs4699700

Positions:

• chr4-99077184-A-G

Variant summary

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

The NM_000671.4(ADH5):​c.345-261T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,142 control chromosomes in the GnomAD database, including 2,216 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 0.16 (2216 hom., cov: 32)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH5	NM_000671.4	c.345-261T>C		intron_variant		ENST00000296412.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH5	ENST00000296412.14	c.345-261T>C		intron_variant		1	NM_000671.4	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24171 AN: 152024 Hom.: 2211 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.159 AC: 24201 AN: 152142 Hom.: 2216 Cov.: 32 AF XY: 0.152 AC XY: 11312 AN XY: 74384

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0483

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.158

Alfa AF: 0.149 Hom.: 317

Bravo AF: 0.168

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.74

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: rs4699700; hg19: chr4-99998335;