Genetic Variant ENSG00000246090:n.3C>A (chr4-99088859-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000500358.6(ENSG00000246090):n.3C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000246090
ENST00000500358.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.318

Publications

22 publications found

Variant links:

Genes affected

ENSG00000246090 (HGNC:):

ENSG00000246090 links:

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)

ADH5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000500358.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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=-0.75).

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>A		non_coding_transcript_exon	Exon 1 of 10
	ADH5	NM_000671.4	MANE Select	c.-159G>T		upstream_gene	N/A	NP_000662.3	P11766

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

298912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

157952

African (AFR)

AF:

0.00

AC:

AN:

8696

American (AMR)

AF:

0.00

AC:

AN:

12624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9772

East Asian (EAS)

AF:

0.00

AC:

AN:

21596

South Asian (SAS)

AF:

0.00

AC:

AN:

21590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

181540

Other (OTH)

AF:

0.00

AC:

AN:

17774

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.34

(source)

DANN

Benign

0.52

PhyloP100

-0.32

PromoterAI

-0.13

Neutral

(source)

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.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over