rs13302577

Variant names:

• chr9-32395898-G-A
• rs13302577
• NM_002197.3:c.-22-9587G>A

Variant summary

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

The NM_002197.3(ACO1):​c.-22-9587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,206 control chromosomes in the GnomAD database, including 6,882 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 0.28 (6882 hom., cov: 33)
• Consequence: ACO1 NM_002197.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 6 publications found

Genes affected

ACO1 (HGNC:117): (aconitase 1) The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5' UTR of ferritin mRNA, and in the 3' UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002197.3. 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
	ACO1	NM_002197.3	MANE Select	c.-22-9587G>A		intron	N/A	NP_002188.1	P21399
	ACO1	NM_001278352.2		c.-23+9456G>A		intron	N/A	NP_001265281.1	P21399
	ACO1	NM_001362840.2		c.-23+9460G>A		intron	N/A	NP_001349769.1	P21399

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACO1	ENST00000309951.8	TSL:1 MANE Select	c.-22-9587G>A		intron	N/A	ENSP00000309477.5	P21399
	ACO1	ENST00000963208.1		c.-22-9587G>A		intron	N/A	ENSP00000633267.1
	ACO1	ENST00000379923.5	TSL:5	c.-23+9460G>A		intron	N/A	ENSP00000369255.1	P21399

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42843 AN: 152088 Hom.: 6875 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.282 AC: 42862 AN: 152206 Hom.: 6882 Cov.: 33 AF XY: 0.278 AC XY: 20722 AN XY: 74424

African (AFR) AF: 0.134 AC: 5558 AN: 41540

American (AMR) AF: 0.358 AC: 5477 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1136 AN: 5168

South Asian (SAS) AF: 0.302 AC: 1456 AN: 4820

European-Finnish (FIN) AF: 0.228 AC: 2416 AN: 10598

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24694 AN: 68006

Other (OTH) AF: 0.303 AC: 639 AN: 2110

Alfa AF: 0.340 Hom.: 5122

Bravo AF: 0.284

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.5
DANN	Benign	0.78
PhyloP100		0.079
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13302577; hg19: chr9-32395896;