4-99085494-A-G

Position:

• chr4-99085494-A-G

Variant summary

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

The NM_000671.4(ADH5):​c.13-278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 303,480 control chromosomes in the GnomAD database, including 92,642 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 (47728 hom., cov: 33)
  • Exomes 𝑓: 0.77 (44914 hom.)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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=-0.91).
• 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.13-278T>C		intron_variant		ENST00000296412.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH5	ENST00000296412.14	c.13-278T>C		intron_variant		1	NM_000671.4	P1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119691 AN: 152128 Hom.: 47676 Cov.: 33

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.757

GnomAD4 exome AF: 0.766 AC: 115859 AN: 151234 Hom.: 44914 Cov.: 2 AF XY: 0.768 AC XY: 59917 AN XY: 78050

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.841

Gnomad4 ASJ exome AF: 0.698

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.876

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.723

Gnomad4 OTH exome AF: 0.765

GnomAD4 genome AF: 0.787 AC: 119804 AN: 152246 Hom.: 47728 Cov.: 33 AF XY: 0.794 AC XY: 59130 AN XY: 74428

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.760

Alfa AF: 0.735 Hom.: 44611

Bravo AF: 0.794

Asia WGS AF: 0.931 AC: 3235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.59

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: rs1154410; hg19: chr4-100006645;