Genetic Variant ENSG00000246090:n.680-10103T>C (chr4-99144442-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000500358.6(ENSG00000246090):n.680-10103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 422,244 control chromosomes in the GnomAD database, including 126,498 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 0.77 ( 45546 hom., cov: 32)

Exomes 𝑓: 0.76 ( 80952 hom. )

Consequence

ENSG00000246090
ENST00000500358.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

Publications

7 publications found

Variant links:

Genes affected

ENSG00000246090 (HGNC:):

ENSG00000246090 links:

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]

ADH4 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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LOC100507053	NR_037884.1		n.680-10103T>C	intron	N/A
ADH4	NM_000670.5	MANE Select	c.-220A>G	upstream_gene	N/A	NP_000661.2	P08319-1
ADH4	NM_001306171.2		c.-311A>G	upstream_gene	N/A	NP_001293100.1	P08319-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ENSG00000246090	ENST00000500358.6	TSL:1	n.680-10103T>C	intron	N/A
ADH4	ENST00000504581.1	TSL:3	n.170-1662A>G	intron	N/A
ENSG00000246090	ENST00000661393.1		n.676+10637T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.766

AC:

116470

AN:

152018

Hom.:

45515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.723

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.786

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.830

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.779

GnomAD4 exome

AF:

0.756

AC:

204143

AN:

270108

Hom.:

80952

AF XY:

0.756

AC XY:

105400

AN XY:

139448

show subpopulations

African (AFR)

AF:

0.726

AC:

5594

AN:

7700

American (AMR)

AF:

0.831

AC:

7888

AN:

9488

Ashkenazi Jewish (ASJ)

AF:

0.801

AC:

7626

AN:

9518

East Asian (EAS)

AF:

0.262

AC:

6282

AN:

24006

South Asian (SAS)

AF:

0.680

AC:

6371

AN:

9374

European-Finnish (FIN)

AF:

0.826

AC:

18249

AN:

22094

Middle Eastern (MID)

AF:

0.767

AC:

1034

AN:

1348

European-Non Finnish (NFE)

AF:

0.814

AC:

137923

AN:

169390

Other (OTH)

AF:

0.766

AC:

13176

AN:

17190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1951

3902

5853

7804

9755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.766

AC:

116549

AN:

152136

Hom.:

45546

Cov.:

AF XY:

0.763

AC XY:

56707

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.723

AC:

30002

AN:

41486

American (AMR)

AF:

0.819

AC:

12522

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

2726

AN:

3470

East Asian (EAS)

AF:

0.266

AC:

1378

AN:

5184

South Asian (SAS)

AF:

0.677

AC:

3266

AN:

4826

European-Finnish (FIN)

AF:

0.830

AC:

8773

AN:

10572

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.813

AC:

55309

AN:

67998

Other (OTH)

AF:

0.780

AC:

1645

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1316

2633

3949

5266

6582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.791

Hom.:

5936

Bravo

AF:

0.763

Asia WGS

AF:

0.590

AC:

2056

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.98

(source)

DANN

Benign

0.40

PhyloP100

-1.5

PromoterAI

-0.065

Neutral

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over