rs6827292

Positions:

• chr4-99071843-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.*574A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,796 control chromosomes in the GnomAD database, including 470 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 0.063 (469 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1 hom.)
• Consequence: ADH5 NM_000671.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH5	NM_000671.4	c.*574A>G		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.*574A>G		3_prime_UTR_variant	9/9	1	NM_000671.4	ENSP00000296412	P1

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9571 AN: 152130 Hom.: 468 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0535

GnomAD4 exome AF: 0.0310 AC: 17 AN: 548 Hom.: 1 Cov.: 0 AF XY: 0.0240 AC XY: 8 AN XY: 334

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0319

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0629 AC: 9583 AN: 152248 Hom.: 469 Cov.: 32 AF XY: 0.0615 AC XY: 4575 AN XY: 74436

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0383

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0411 Hom.: 174

Bravo AF: 0.0663

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.45

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: rs6827292; hg19: chr4-99992994;