ENST00000500358.6:n.121C>G

Variant names:

• chr4-99088977-C-G
• rs2602899
• ENST00000500358.6:n.121C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000500358.6(ENSG00000246090):​n.121C>G 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 0.0000109 in 276,390 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.121C>G		non_coding_transcript_exon	Exon 1 of 10
	ADH5	NM_000671.4	MANE Select	c.-277G>C		upstream_gene	N/A	NP_000662.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.121C>G		non_coding_transcript_exon	Exon 1 of 10
	ENSG00000246090	ENST00000499178.3	TSL:3	n.108C>G		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000246090	ENST00000661393.1		n.118C>G		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000109 AC: 3 AN: 276390 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 143712

African (AFR) AF: 0.00 AC: 0 AN: 7406

American (AMR) AF: 0.00 AC: 0 AN: 8886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9620

East Asian (EAS) AF: 0.00 AC: 0 AN: 22334

South Asian (SAS) AF: 0.00 AC: 0 AN: 16472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1308

European-Non Finnish (NFE) AF: 0.0000176 AC: 3 AN: 170162

Other (OTH) AF: 0.00 AC: 0 AN: 17360

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1866

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.88
DANN	Benign	0.47
PhyloP100		-0.92
PromoterAI		-0.067	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2602899; hg19: chr4-100010128;