dbSNP rs2232873: MIOX:c.-229G>A (chr22-50486669-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017584.6(MIOX):c.-229G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 623,754 control chromosomes in the GnomAD database, including 11,561 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 0.17 ( 3124 hom., cov: 33)

Exomes 𝑓: 0.15 ( 8437 hom. )

Consequence

MIOX
NM_017584.6 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

7 publications found

Variant links:

COSMIC-nc: COSV53315000

Genes affected

MIOX (HGNC:14522): (myo-inositol oxygenase) Enables ferric iron binding activity and inositol oxygenase activity. Involved in inositol catabolic process. Predicted to be located in cytoplasm and inclusion body. [provided by Alliance of Genome Resources, Apr 2022]

MIOX links:

ADM2 (HGNC:28898): (adrenomedullin 2) This gene encodes a member of the calcitonin gene-related peptide (CGRP)/calcitonin family of hormones that play a role in the regulation of cardiovascular homeostasis, prolactin release, anti-diuresis, anti-natriuresis, and regulation of food and water intake. The encoded protein is proteolytically processed to generate one or more biologically active peptides. [provided by RefSeq, Jul 2015]

ADM2 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOX	NM_017584.6 link	c.-229G>A		upstream_gene_variant		ENST00000216075.11	NP_060054.4	Q9UGB7-1
ADM2	NM_001253845.2 link	c.*3766G>A		downstream_gene_variant		ENST00000395737.2	NP_001240774.1	Q7Z4H4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIOX	ENST00000216075.11 link	c.-229G>A		upstream_gene_variant		1	NM_017584.6	ENSP00000216075.6		Q9UGB7-1
ADM2	ENST00000395737.2 link	c.*3766G>A		downstream_gene_variant		1	NM_001253845.2	ENSP00000379086.1		Q7Z4H4

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26307

AN:

152060

Hom.:

3114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.0750

Gnomad OTH

AF:

0.193

GnomAD4 exome

AF:

0.151

AC:

71257

AN:

471576

Hom.:

8437

AF XY:

0.157

AC XY:

39309

AN XY:

250182

show subpopulations

African (AFR)

AF:

0.244

AC:

3266

AN:

13364

American (AMR)

AF:

0.307

AC:

7680

AN:

25024

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

2722

AN:

14660

East Asian (EAS)

AF:

0.392

AC:

12080

AN:

30838

South Asian (SAS)

AF:

0.299

AC:

14925

AN:

49890

European-Finnish (FIN)

AF:

0.141

AC:

4141

AN:

29434

Middle Eastern (MID)

AF:

0.214

AC:

505

AN:

2358

European-Non Finnish (NFE)

AF:

0.0776

AC:

21683

AN:

279330

Other (OTH)

AF:

0.159

AC:

4255

AN:

26678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2637

5274

7912

10549

13186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.173

AC:

26342

AN:

152178

Hom.:

3124

Cov.:

AF XY:

0.186

AC XY:

13803

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.242

AC:

10043

AN:

41504

American (AMR)

AF:

0.296

AC:

4521

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

657

AN:

3472

East Asian (EAS)

AF:

0.434

AC:

2241

AN:

5164

South Asian (SAS)

AF:

0.320

AC:

1543

AN:

4824

European-Finnish (FIN)

AF:

0.166

AC:

1755

AN:

10604

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0749

AC:

5096

AN:

68008

Other (OTH)

AF:

0.194

AC:

410

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1033

2066

3098

4131

5164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.121

Hom.:

3999

Bravo

AF:

0.184

Asia WGS

AF:

0.339

AC:

1174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.39

(source)

DANN

Benign

0.68

PhyloP100

-1.1

PromoterAI

-0.012

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over