dbSNP rs2602899: ENSG00000246090:n.121C>G (chr4-99088977-C-G) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.923

Publications

4 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:

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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=-0.78).

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	P11766

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
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.:

GnomAD4 exome

AF:

0.0000109

AC:

AN:

276390

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

143712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7406

American (AMR)

AF:

0.00

AC:

AN:

8886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9620

East Asian (EAS)

AF:

0.00

AC:

AN:

22334

South Asian (SAS)

AF:

0.00

AC:

AN:

16472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1308

European-Non Finnish (NFE)

AF:

0.0000176

AC:

AN:

170162

Other (OTH)

AF:

0.00

AC:

AN:

17360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

(source)

DANN

Benign

0.47

PhyloP100

-0.92

PromoterAI

-0.067

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

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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