Genetic Variant ADH6:c.19-115C>T (chr4-99216377-G-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 NM_001102470.2(ADH6):c.19-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 320,674 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 0.0 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADH6
NM_001102470.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.734

Publications

7 publications found

Variant links:

Genes affected

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:

ENSG00000246090 (HGNC:):

ENSG00000246090 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=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102470.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADH6	NM_001102470.2	MANE Select	c.19-115C>T	intron	N/A	NP_001095940.1
ADH6	NM_000672.4		c.19-115C>T	intron	N/A	NP_000663.1
LOC100507053	NR_037884.1		n.3789+11946G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADH6	ENST00000394899.6	TSL:2 MANE Select	c.19-115C>T	intron	N/A	ENSP00000378359.2
ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+11946G>A	intron	N/A
ADH6	ENST00000237653.11	TSL:5	c.19-115C>T	intron	N/A	ENSP00000237653.7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150736

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

320674

Hom.:

AF XY:

0.0000181

AC XY:

AN XY:

165362

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

8582

American (AMR)

AF:

0.00

AC:

AN:

9024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9832

East Asian (EAS)

AF:

0.0000839

AC:

AN:

23836

South Asian (SAS)

AF:

0.00

AC:

AN:

8406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1530

European-Non Finnish (NFE)

AF:

0.00000469

AC:

AN:

213052

Other (OTH)

AF:

0.0000550

AC:

AN:

18184

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0261725), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

150736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73458

African (AFR)

AF:

0.00

AC:

AN:

41022

American (AMR)

AF:

0.00

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67724

Other (OTH)

AF:

0.00

AC:

AN:

2084

Alfa

AF:

0.00

Hom.:

1581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.0

(source)

DANN

Benign

0.90

PhyloP100

-0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over