4-99088859-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

ADH5 Gene-Disease associations (from GenCC):

• AMED syndrome, digenic

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500358.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100507053	NR_037884.1		n.3C>T		non_coding_transcript_exon	Exon 1 of 10
	ADH5	NM_000671.4	MANE Select	c.-159G>A		upstream_gene	N/A	NP_000662.3	P11766

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3C>T		non_coding_transcript_exon	Exon 1 of 10
	ENSG00000246090	ENST00000670724.2		n.55C>T		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000246090	ENST00000671105.1		n.27C>T		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.663 AC: 5725 AN: 8630

American (AMR) AF: 0.796 AC: 10010 AN: 12572

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 6209 AN: 9698

East Asian (EAS) AF: 0.998 AC: 21554 AN: 21596

South Asian (SAS) AF: 0.816 AC: 17506 AN: 21458

European-Finnish (FIN) AF: 0.695 AC: 16583 AN: 23870

Middle Eastern (MID) AF: 0.717 AC: 924 AN: 1288

European-Non Finnish (NFE) AF: 0.649 AC: 116854 AN: 180156

Other (OTH) AF: 0.692 AC: 12214 AN: 17660

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

African (AFR) AF: 0.682 AC: 28063 AN: 41130

American (AMR) AF: 0.757 AC: 11528 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2344 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5080 AN: 5090

South Asian (SAS) AF: 0.870 AC: 4177 AN: 4802

European-Finnish (FIN) AF: 0.731 AC: 7589 AN: 10382

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46168 AN: 67836

Other (OTH) AF: 0.697 AC: 1465 AN: 2102

Alfa AF: 0.696 Hom.: 115839

Bravo AF: 0.711

Asia WGS AF: 0.913 AC: 3171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.46
DANN	Benign	0.80
PhyloP100		-0.32
PromoterAI		-0.072	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1154400;

hg19: chr4-100010010;

COSMIC: COSV56449194;