rs650727

Positions:

• chr18-11989970-G-A

Variant summary

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

The NM_014214.3(IMPA2):​c.96+8205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,008 control chromosomes in the GnomAD database, including 12,284 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 0.38 (12284 hom., cov: 32)
• Consequence: IMPA2 NM_014214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPA2	NM_014214.3	c.96+8205G>A		intron_variant		ENST00000269159.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPA2	ENST00000269159.8	c.96+8205G>A		intron_variant		1	NM_014214.3	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57501 AN: 151890 Hom.: 12246 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.379 AC: 57601 AN: 152008 Hom.: 12284 Cov.: 32 AF XY: 0.384 AC XY: 28510 AN XY: 74302

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.351

Alfa AF: 0.345 Hom.: 1193

Bravo AF: 0.386

Asia WGS AF: 0.552 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.36

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: rs650727; hg19: chr18-11989969;