4-99083500-C-T

Variant names:

• chr4-99083500-C-T
• rs1154411
• NM_000671.4:c.115-1384G>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.115-1384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 150,686 control chromosomes in the GnomAD database, including 47,139 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 (47139 hom., cov: 25)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 1 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4	c.115-1384G>A		intron_variant	Intron 2 of 8	ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.115-1384G>A		intron_variant	Intron 2 of 8	1	NM_000671.4	ENSP00000296412.8

Frequencies

GnomAD3 genomes AF: 0.785 AC: 118262 AN: 150570 Hom.: 47089 Cov.: 25

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.786 AC: 118372 AN: 150686 Hom.: 47139 Cov.: 25 AF XY: 0.794 AC XY: 58314 AN XY: 73478

African (AFR) AF: 0.905 AC: 37191 AN: 41116

American (AMR) AF: 0.773 AC: 11675 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2363 AN: 3462

East Asian (EAS) AF: 0.987 AC: 5015 AN: 5080

South Asian (SAS) AF: 0.866 AC: 4114 AN: 4748

European-Finnish (FIN) AF: 0.795 AC: 8194 AN: 10312

Middle Eastern (MID) AF: 0.755 AC: 219 AN: 290

European-Non Finnish (NFE) AF: 0.703 AC: 47500 AN: 67576

Other (OTH) AF: 0.750 AC: 1565 AN: 2088

Alfa AF: 0.743 Hom.: 5002

Bravo AF: 0.789

Asia WGS AF: 0.906 AC: 3148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.14
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: rs1154411; hg19: chr4-100004651;