Genetic Variant ADH6:c.*660G>C (chr4-99203559-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001102470.2(ADH6):c.*660G>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 0.634 in 151,916 control chromosomes in the GnomAD database, including 32,060 homozygotes. 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 0.63 ( 32057 hom., cov: 31)

Exomes 𝑓: 0.55 ( 3 hom. )

Consequence

ADH6
NM_001102470.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.318

Publications

9 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

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	UniProt
ADH6	NM_001102470.2	MANE Select	c.*660G>C	3_prime_UTR	Exon 9 of 9	NP_001095940.1	P28332-2
ADH6	NM_000672.4		c.*1362G>C	3_prime_UTR	Exon 8 of 8	NP_000663.1	P28332-1
ADH6	NR_132990.2		n.1523G>C	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADH6	ENST00000394899.6	TSL:2 MANE Select	c.*660G>C	3_prime_UTR	Exon 9 of 9	ENSP00000378359.2	P28332-2
ENSG00000246090	ENST00000500358.6	TSL:1	n.3715-798C>G	intron	N/A
ADH6	ENST00000881183.1		c.*660G>C	3_prime_UTR	Exon 9 of 9	ENSP00000551242.1

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96197

AN:

151776

Hom.:

32005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.828

Gnomad AMI

AF:

0.585

Gnomad AMR

AF:

0.630

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.619

GnomAD4 exome

AF:

0.550

AC:

AN:

Hom.:

Cov.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.634

AC:

96304

AN:

151896

Hom.:

32057

Cov.:

AF XY:

0.632

AC XY:

46917

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.829

AC:

34358

AN:

41464

American (AMR)

AF:

0.630

AC:

9596

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

2018

AN:

3468

East Asian (EAS)

AF:

0.879

AC:

4537

AN:

5160

South Asian (SAS)

AF:

0.571

AC:

2750

AN:

4814

European-Finnish (FIN)

AF:

0.499

AC:

5264

AN:

10546

Middle Eastern (MID)

AF:

0.534

AC:

156

AN:

292

European-Non Finnish (NFE)

AF:

0.527

AC:

35794

AN:

67894

Other (OTH)

AF:

0.617

AC:

1299

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1664

3328

4993

6657

8321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.568

Hom.:

2997

Bravo

AF:

0.654

Asia WGS

AF:

0.646

AC:

2246

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.2

(source)

DANN

Benign

0.60

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over