rs1020294

Positions:

• chr18-12017344-A-G

Variant summary

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

The NM_014214.3(IMPA2):​c.490+2971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,024 control chromosomes in the GnomAD database, including 17,239 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 0.45 (17239 hom., cov: 32)
• Consequence: IMPA2 NM_014214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

Genes affected

IMPA2 (HGNC:6051): (inositol monophosphatase 2) This locus encodes an inositol monophosphatase. The encoded protein catalyzes the dephosphoylration of inositol monophosphate and plays an important role in phosphatidylinositol signaling. This locus may be associated with susceptibility to bipolar disorder. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPA2	NM_014214.3	c.490+2971A>G		intron_variant		ENST00000269159.8
IMPA2	XM_011525659.4	c.442+2971A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPA2	ENST00000269159.8	c.490+2971A>G		intron_variant		1	NM_014214.3	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67654 AN: 151906 Hom.: 17239 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.445 AC: 67679 AN: 152024 Hom.: 17239 Cov.: 32 AF XY: 0.441 AC XY: 32765 AN XY: 74292

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.501

Alfa AF: 0.555 Hom.: 48866

Bravo AF: 0.426

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.69

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: rs1020294; hg19: chr18-12017343;