rs727563

Positions:

• chr22-41471373-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098.3(ACO2):​c.36+2191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 150,844 control chromosomes in the GnomAD database, including 29,711 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 0.59 (29711 hom., cov: 31)
• Consequence: ACO2 NM_001098.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786

Genes affected

ACO2 (HGNC:118): (aconitase 2) The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]

ACO2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACO2	NM_001098.3	c.36+2191C>T		intron_variant		ENST00000216254.9	NP_001089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACO2	ENST00000216254.9	c.36+2191C>T		intron_variant		1	NM_001098.3	ENSP00000216254.4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89438 AN: 150724 Hom.: 29711 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.593 AC: 89433 AN: 150844 Hom.: 29711 Cov.: 31 AF XY: 0.586 AC XY: 43236 AN XY: 73764

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.616

Alfa AF: 0.685 Hom.: 7278

Bravo AF: 0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.3
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

Other links and lift over

dbSNP: rs727563; hg19: chr22-41867377;