4-99088859-C-T

Variant names:

• chr4-99088859-C-T
• rs1154400
• ENST00000500358.6:n.3C>T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.3C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 448,168 control chromosomes in the GnomAD database, including 113,317 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 0.71 (38418 hom., cov: 27)
  • Exomes 𝑓: 0.70 (74899 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

Genes affected

ENSG00000246090 (HGNC:):

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.3C>T		non_coding_transcript_exon_variant	Exon 1 of 10
ADH5	NM_000671.4	c.-159G>A		upstream_gene_variant		ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.-159G>A		upstream_gene_variant		1	NM_000671.4	ENSP00000296412.8

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107131 AN: 151122 Hom.: 38384 Cov.: 27

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.699 AC: 207579 AN: 296928 Hom.: 74899 Cov.: 4 AF XY: 0.702 AC XY: 110096 AN XY: 156872

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.816

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.692

GnomAD4 genome AF: 0.709 AC: 107220 AN: 151240 Hom.: 38418 Cov.: 27 AF XY: 0.718 AC XY: 53021 AN XY: 73820

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.697

Alfa AF: 0.692 Hom.: 70087

Bravo AF: 0.711

Asia WGS AF: 0.913 AC: 3171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.46
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1154400; hg19: chr4-100010010; COSMIC: COSV56449194;