Variant chr9-32425912-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002197.3(ACO1):c.1263A>G(p.Glu421Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,612,936 control chromosomes in the GnomAD database, including 100,381 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 0.33 ( 8843 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91538 hom. )

Consequence

ACO1
NM_002197.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0820

Variant links:

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]

ACO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=-0.082 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACO1	NM_002197.3 link	c.1263A>G	p.Glu421Glu	synonymous_variant	11/21	ENST00000309951.8	NP_002188.1	P21399V9HWB7
ACO1	NM_001278352.2 link	c.1263A>G	p.Glu421Glu	synonymous_variant	12/22		NP_001265281.1	P21399V9HWB7Q9HBB2
ACO1	NM_001362840.2 link	c.1263A>G	p.Glu421Glu	synonymous_variant	12/22		NP_001349769.1
ACO1	XM_047423430.1 link	c.1287A>G	p.Glu429Glu	synonymous_variant	11/21		XP_047279386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACO1	ENST00000309951.8 link	c.1263A>G	p.Glu421Glu	synonymous_variant	11/21	1	NM_002197.3	ENSP00000309477.5	P21399
ACO1	ENST00000379923.5 link	c.1263A>G	p.Glu421Glu	synonymous_variant	12/22	5		ENSP00000369255.1	P21399
ACO1	ENST00000541043.5 link	c.1263A>G	p.Glu421Glu	synonymous_variant	12/22	5		ENSP00000438733.2	P21399

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50525

AN:

151940

Hom.:

8828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.346

AC:

86780

AN:

250774

Hom.:

15756

AF XY:

0.344

AC XY:

46601

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.547

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.351

AC:

513221

AN:

1460878

Hom.:

91538

Cov.:

AF XY:

0.350

AC XY:

254345

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.510

Gnomad4 SAS exome

AF:

0.291

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.333

AC:

50574

AN:

152058

Hom.:

8843

Cov.:

AF XY:

0.333

AC XY:

24736

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.349

Hom.:

15884

Bravo

AF:

0.332

Asia WGS

AF:

0.409

AC:

1421

AN:

3478

EpiCase

AF:

0.356

EpiControl

AF:

0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.3

DANN

Benign

0.48

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over