rs2232873

Variant names:

• chr22-50486669-G-A
• rs2232873
• NM_017584.6:c.-229G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50486669-G-A
• chr22-50486669-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 7 publications found

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]

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017584.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIOX	NM_017584.6	MANE Select	c.-229G>A		upstream_gene	N/A	NP_060054.4
	ADM2	NM_001253845.2	MANE Select	c.*3766G>A		downstream_gene	N/A	NP_001240774.1	Q7Z4H4
	ADM2	NM_001369882.1		c.*3766G>A		downstream_gene	N/A	NP_001356811.1	Q7Z4H4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIOX	ENST00000216075.11	TSL:1 MANE Select	c.-229G>A		upstream_gene	N/A	ENSP00000216075.6	Q9UGB7-1
	MIOX	ENST00000395732.7	TSL:1	c.-229G>A		upstream_gene	N/A	ENSP00000379081.3	A6PVH2
	MIOX	ENST00000395733.7	TSL:1	c.-229G>A		upstream_gene	N/A	ENSP00000379082.3	Q9UGB7-2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26307 AN: 152060 Hom.: 3114 Cov.: 33

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

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

GnomAD4 genome AF: 0.173 AC: 26342 AN: 152178 Hom.: 3124 Cov.: 33 AF XY: 0.186 AC XY: 13803 AN XY: 74404

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: 64 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5096 AN: 68008

Other (OTH) AF: 0.194 AC: 410 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.68
PhyloP100		-1.1
PromoterAI		-0.012	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2232873; hg19: chr22-50925098; COSMIC: COSV53315000;