Variant 9-32450189-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002197.3(ACO1):c.*78T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,149,134 control chromosomes in the GnomAD database, including 83,903 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 0.39 ( 11793 hom., cov: 31)

Exomes 𝑓: 0.38 ( 72110 hom. )

Consequence

ACO1
NM_002197.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.420

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ACO1	NM_002197.3 linkuse as main transcript	c.*78T>C	3_prime_UTR_variant	21/21	ENST00000309951.8	NP_002188.1
ACO1	NM_001278352.2 linkuse as main transcript	c.*78T>C	3_prime_UTR_variant	22/22		NP_001265281.1
ACO1	NM_001362840.2 linkuse as main transcript	c.*78T>C	3_prime_UTR_variant	22/22		NP_001349769.1
ACO1	XM_047423430.1 linkuse as main transcript	c.*78T>C	3_prime_UTR_variant	21/21		XP_047279386.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ACO1	ENST00000309951.8 linkuse as main transcript	c.*78T>C	3_prime_UTR_variant	21/21	1	NM_002197.3	ENSP00000309477	P1
ACO1	ENST00000379923.5 linkuse as main transcript	c.*78T>C	3_prime_UTR_variant	22/22	5		ENSP00000369255	P1
ACO1	ENST00000541043.5 linkuse as main transcript	c.*78T>C	3_prime_UTR_variant	22/22	5		ENSP00000438733	P1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59495

AN:

151764

Hom.:

11773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.360

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.411

GnomAD3 exomes

AF:

0.384

AC:

91771

AN:

238836

Hom.:

17998

AF XY:

0.376

AC XY:

49021

AN XY:

130388

show subpopulations

Gnomad AFR exome

AF:

0.424

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.551

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.376

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.378

AC:

376574

AN:

997252

Hom.:

72110

Cov.:

AF XY:

0.372

AC XY:

191843

AN XY:

516172

show subpopulations

Gnomad4 AFR exome

AF:

0.408

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.392

AC:

59559

AN:

151882

Hom.:

11793

Cov.:

AF XY:

0.390

AC XY:

28966

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.411

Gnomad4 AMR

AF:

0.382

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.524

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.390

Hom.:

12222

Bravo

AF:

0.400

Asia WGS

AF:

0.399

AC:

1388

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.43

DANN

Benign

0.23

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