rs7022554

Variant summary

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

The NM_002197.3(ACO1):​c.2100-234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 669,714 control chromosomes in the GnomAD database, including 105,270 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 0.56 ( 23979 hom., cov: 32)
Exomes 𝑓: 0.56 ( 81291 hom. )

Consequence

ACO1
NM_002197.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.292
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]

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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=-0.91).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACO1NM_002197.3 linkuse as main transcriptc.2100-234A>G intron_variant ENST00000309951.8 NP_002188.1 P21399V9HWB7
ACO1NM_001278352.2 linkuse as main transcriptc.2100-234A>G intron_variant NP_001265281.1 P21399V9HWB7Q9HBB2
ACO1NM_001362840.2 linkuse as main transcriptc.2100-234A>G intron_variant NP_001349769.1
ACO1XM_047423430.1 linkuse as main transcriptc.2124-234A>G intron_variant XP_047279386.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACO1ENST00000309951.8 linkuse as main transcriptc.2100-234A>G intron_variant 1 NM_002197.3 ENSP00000309477.5 P21399
ACO1ENST00000379923.5 linkuse as main transcriptc.2100-234A>G intron_variant 5 ENSP00000369255.1 P21399
ACO1ENST00000541043.5 linkuse as main transcriptc.2100-234A>G intron_variant 5 ENSP00000438733.2 P21399

Frequencies

GnomAD3 genomes
AF:
0.561
AC:
85212
AN:
151910
Hom.:
23935
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.576
Gnomad AMI
AF:
0.532
Gnomad AMR
AF:
0.499
Gnomad ASJ
AF:
0.550
Gnomad EAS
AF:
0.552
Gnomad SAS
AF:
0.589
Gnomad FIN
AF:
0.531
Gnomad MID
AF:
0.541
Gnomad NFE
AF:
0.570
Gnomad OTH
AF:
0.551
GnomAD3 exomes
AF:
0.545
AC:
74495
AN:
136642
Hom.:
20577
AF XY:
0.551
AC XY:
40735
AN XY:
73898
show subpopulations
Gnomad AFR exome
AF:
0.575
Gnomad AMR exome
AF:
0.447
Gnomad ASJ exome
AF:
0.568
Gnomad EAS exome
AF:
0.565
Gnomad SAS exome
AF:
0.571
Gnomad FIN exome
AF:
0.532
Gnomad NFE exome
AF:
0.568
Gnomad OTH exome
AF:
0.563
GnomAD4 exome
AF:
0.557
AC:
288561
AN:
517686
Hom.:
81291
Cov.:
4
AF XY:
0.560
AC XY:
157703
AN XY:
281560
show subpopulations
Gnomad4 AFR exome
AF:
0.576
Gnomad4 AMR exome
AF:
0.453
Gnomad4 ASJ exome
AF:
0.565
Gnomad4 EAS exome
AF:
0.499
Gnomad4 SAS exome
AF:
0.573
Gnomad4 FIN exome
AF:
0.536
Gnomad4 NFE exome
AF:
0.572
Gnomad4 OTH exome
AF:
0.560
GnomAD4 genome
AF:
0.561
AC:
85305
AN:
152028
Hom.:
23979
Cov.:
32
AF XY:
0.560
AC XY:
41594
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.576
Gnomad4 AMR
AF:
0.499
Gnomad4 ASJ
AF:
0.550
Gnomad4 EAS
AF:
0.552
Gnomad4 SAS
AF:
0.589
Gnomad4 FIN
AF:
0.531
Gnomad4 NFE
AF:
0.570
Gnomad4 OTH
AF:
0.556
Alfa
AF:
0.560
Hom.:
15535
Bravo
AF:
0.558
Asia WGS
AF:
0.570
AC:
1985
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
2.1
DANN
Benign
0.32
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs7022554; hg19: chr9-32436014; COSMIC: COSV59381132; API