Genetic Variant ENST00000500358.6:n.680-10187T>G (chr4-99144358-T-G) – 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.680-10187T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 832,468 control chromosomes in the GnomAD database, including 155,044 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 0.50 ( 21619 hom., cov: 31)

Exomes 𝑓: 0.62 ( 133425 hom. )

Consequence

ENSG00000246090
ENST00000500358.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

Publications

65 publications found

Variant links:

COSMIC-nc: COSV55501258

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=-0.72).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 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
LOC100507053	NR_037884.1		n.680-10187T>G	intron	N/A
ADH4	NM_000670.5	MANE Select	c.-136A>C	upstream_gene	N/A	NP_000661.2
ADH4	NM_001306171.2		c.-227A>C	upstream_gene	N/A	NP_001293100.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ENSG00000246090	ENST00000500358.6	TSL:1	n.680-10187T>G	intron	N/A
ADH4	ENST00000504581.1	TSL:3	n.170-1578A>C	intron	N/A
ENSG00000246090	ENST00000661393.1		n.676+10553T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75940

AN:

151898

Hom.:

21616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.799

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.515

GnomAD4 exome

AF:

0.615

AC:

418577

AN:

680452

Hom.:

133425

AF XY:

0.625

AC XY:

225031

AN XY:

359780

show subpopulations

African (AFR)

AF:

0.227

AC:

4056

AN:

17852

American (AMR)

AF:

0.421

AC:

14639

AN:

34738

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

11127

AN:

19036

East Asian (EAS)

AF:

0.848

AC:

28868

AN:

34056

South Asian (SAS)

AF:

0.799

AC:

48986

AN:

61302

European-Finnish (FIN)

AF:

0.575

AC:

22590

AN:

39306

Middle Eastern (MID)

AF:

0.618

AC:

2469

AN:

3996

European-Non Finnish (NFE)

AF:

0.609

AC:

265502

AN:

436174

Other (OTH)

AF:

0.598

AC:

20340

AN:

33992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

7335

14670

22006

29341

36676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3960

7920

11880

15840

19800

<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:

0.500

AC:

75962

AN:

152016

Hom.:

21619

Cov.:

AF XY:

0.507

AC XY:

37686

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.233

AC:

9654

AN:

41478

American (AMR)

AF:

0.454

AC:

6934

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2009

AN:

3468

East Asian (EAS)

AF:

0.857

AC:

4435

AN:

5174

South Asian (SAS)

AF:

0.799

AC:

3852

AN:

4820

European-Finnish (FIN)

AF:

0.578

AC:

6100

AN:

10554

Middle Eastern (MID)

AF:

0.651

AC:

190

AN:

292

European-Non Finnish (NFE)

AF:

0.606

AC:

41142

AN:

67942

Other (OTH)

AF:

0.519

AC:

1096

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1671

3343

5014

6686

8357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.551

Hom.:

42732

Bravo

AF:

0.471

Asia WGS

AF:

0.744

AC:

2585

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.7

PromoterAI

-0.26

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