rs1803037

Positions:

• chr4-99072000-C-T

Variant summary

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

The NM_000671.4(ADH5):​c.*417G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 165,838 control chromosomes in the GnomAD database, including 592 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 0.082 (544 hom., cov: 32)
  • Exomes 𝑓: 0.078 (48 hom.)
• Consequence: ADH5 NM_000671.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH5	NM_000671.4	c.*417G>A		3_prime_UTR_variant	9/9	ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.*417G>A		3_prime_UTR_variant	9/9	1	NM_000671.4	ENSP00000296412	P1

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 12424 AN: 152020 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0982

GnomAD4 exome AF: 0.0782 AC: 1071 AN: 13700 Hom.: 48 Cov.: 0 AF XY: 0.0739 AC XY: 526 AN XY: 7116

Gnomad4 AFR exome AF: 0.0829

Gnomad4 AMR exome AF: 0.0830

Gnomad4 ASJ exome AF: 0.0907

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0293

Gnomad4 FIN exome AF: 0.0406

Gnomad4 NFE exome AF: 0.0890

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.0817 AC: 12433 AN: 152138 Hom.: 544 Cov.: 32 AF XY: 0.0770 AC XY: 5724 AN XY: 74382

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.0894

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0972

Alfa AF: 0.0994 Hom.: 1353

Bravo AF: 0.0855

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.52

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: rs1803037; hg19: chr4-99993151;