4-99081221-C-T

Position:

• chr4-99081221-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.344+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 516,232 control chromosomes in the GnomAD database, including 132,969 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 0.69 (35779 hom., cov: 26)
  • Exomes 𝑓: 0.73 (97190 hom.)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH5	NM_000671.4	c.344+144G>A		intron_variant		ENST00000296412.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH5	ENST00000296412.14	c.344+144G>A		intron_variant		1	NM_000671.4	P1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 103381 AN: 150410 Hom.: 35762 Cov.: 26

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.671

GnomAD4 exome AF: 0.730 AC: 266910 AN: 365714 Hom.: 97190 AF XY: 0.737 AC XY: 148401 AN XY: 201240

Gnomad4 AFR exome AF: 0.670

Gnomad4 AMR exome AF: 0.754

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.841

Gnomad4 FIN exome AF: 0.710

Gnomad4 NFE exome AF: 0.692

Gnomad4 OTH exome AF: 0.719

GnomAD4 genome AF: 0.687 AC: 103435 AN: 150518 Hom.: 35779 Cov.: 26 AF XY: 0.697 AC XY: 51181 AN XY: 73442

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.675

Alfa AF: 0.684 Hom.: 10960

Bravo AF: 0.681

Asia WGS AF: 0.890 AC: 3092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.60

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: rs896992; hg19: chr4-100002372;