4-99086719-C-A

Variant names:

• chr4-99086719-C-A
• rs1154409
• NM_000671.4:c.13-1503G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000671.4(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 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 0 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	NM_000671.4	MANE Select	c.13-1503G>T		intron	N/A	NP_000662.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	ENST00000296412.14	TSL:1 MANE Select	c.13-1503G>T		intron	N/A	ENSP00000296412.8
	ADH5	ENST00000626055.2	TSL:5	c.13-1503G>T		intron	N/A	ENSP00000487496.1
	ADH5	ENST00000502386.1	TSL:5	n.26-1086G>T		intron	N/A

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

African (AFR) AF: 0.0314 AC: 1293 AN: 41204

American (AMR) AF: 0.106 AC: 1610 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 612 AN: 3458

East Asian (EAS) AF: 0.723 AC: 3649 AN: 5046

South Asian (SAS) AF: 0.280 AC: 1342 AN: 4792

European-Finnish (FIN) AF: 0.0803 AC: 843 AN: 10492

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.127 AC: 8599 AN: 67834

Other (OTH) AF: 0.137 AC: 287 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.58
PhyloP100		-3.0
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: rs1154409; hg19: chr4-100007870;