Genetic Variant ENSG00000246090:n.3715-1738C>G (chr4-99202619-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 ENST00000881182.1(ADH6):c.*1600G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000732 in 396,348 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: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

ADH6
ENST00000881182.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.398

Publications

7 publications found

Variant links:

Genes affected

ENSG00000246090 (HGNC:):

ENSG00000246090 links:

ADH6 (HGNC:255): (alcohol dehydrogenase 6 (class V)) This gene encodes class V alcohol dehydrogenase, which is 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. This gene is expressed in the stomach as well as in the liver, and it contains a glucocorticoid response element upstream of its 5' UTR, which is a steroid hormone receptor binding site. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ADH6 links:

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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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000881182.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LOC100507053	NR_037884.1		n.3715-1738C>G	intron	N/A
ADH6	NM_001102470.2	MANE Select	c.*1600G>C	downstream_gene	N/A	NP_001095940.1	P28332-2
ADH6	NM_000672.4		c.*2302G>C	downstream_gene	N/A	NP_000663.1	P28332-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENSG00000246090	ENST00000500358.6	TSL:1	n.3715-1738C>G	intron	N/A
ADH6	ENST00000881182.1		c.*1600G>C	3_prime_UTR	Exon 8 of 8	ENSP00000551241.1
ENSG00000246090	ENST00000506160.1	TSL:4	n.333-1738C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000900

AC:

AN:

244418

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

123926

show subpopulations

African (AFR)

AF:

0.000141

AC:

AN:

7112

American (AMR)

AF:

0.00

AC:

AN:

7402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9156

East Asian (EAS)

AF:

0.00

AC:

AN:

22872

South Asian (SAS)

AF:

0.00

AC:

AN:

2806

European-Finnish (FIN)

AF:

0.0000482

AC:

AN:

20746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1276

European-Non Finnish (NFE)

AF:

0.000128

AC:

AN:

156770

Other (OTH)

AF:

0.00

AC:

AN:

16278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151930

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41344

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000946

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

83184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.69

(source)

DANN

Benign

0.34

PhyloP100

-0.40

Splicing

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over