Genetic Variant NM_001102470.2:c.1017G>A (chr4-99205011-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001102470.2(ADH6):c.1017G>A(p.Glu339Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,366 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: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ADH6
NM_001102470.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193

Publications

0 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 -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13290322).

BP7

Synonymous conserved (PhyloP=-0.193 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH6	NM_001102470.2 link	c.1017G>A	p.Glu339Glu	synonymous_variant	Exon 8 of 9	ENST00000394899.6	NP_001095940.1	P28332-2Q8IUN7
ADH6	NM_000672.4 link	c.1017G>A	p.Glu339Glu	synonymous_variant	Exon 8 of 8		NP_000663.1	P28332-1Q8IUN7
ADH6	NR_132990.2 link	n.752G>A		non_coding_transcript_exon_variant	Exon 6 of 7
LOC100507053	NR_037884.1 link	n.3789+580C>T		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH6	ENST00000394899.6 link	c.1017G>A	p.Glu339Glu	synonymous_variant	Exon 8 of 9	2	NM_001102470.2	ENSP00000378359.2		P28332-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246368

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33004

American (AMR)

AF:

0.00

AC:

AN:

44066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25984

East Asian (EAS)

AF:

0.00

AC:

AN:

39266

South Asian (SAS)

AF:

0.00

AC:

AN:

85422

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109432

Other (OTH)

AF:

0.00

AC:

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.7

(source)

DANN

Benign

0.94

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.35

M_CAP

Benign

0.0058

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.98

PhyloP100

-0.19

PROVEAN

Benign

0.020

REVEL

Benign

0.028

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.25

MutPred

0.42

Gain of ubiquitination at R294 (P = 0.0351);

MVP

0.44

ClinPred

0.17

GERP RS

2.0

Mutation Taster

=90/10

polymorphism

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over