chr18-11994599-C-A

Variant names:

• chr18-11994599-C-A
• rs669838
• NM_014214.3:c.97-4455C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014214.3(IMPA2):​c.97-4455C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,076 control chromosomes in the GnomAD database, including 17,817 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 0.46 (17817 hom., cov: 33)
• Consequence: IMPA2 NM_014214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 8 publications found

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]

ENSG00000266955 (HGNC:58565):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPA2	NM_014214.3	MANE Select	c.97-4455C>A		intron	N/A	NP_055029.1	O14732-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPA2	ENST00000269159.8	TSL:1 MANE Select	c.97-4455C>A		intron	N/A	ENSP00000269159.3	O14732-1
	IMPA2	ENST00000383376.9	TSL:1	n.97-4455C>A		intron	N/A	ENSP00000372867.4	Q6PIP6
	IMPA2	ENST00000886600.1		c.97-4455C>A		intron	N/A	ENSP00000556659.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69287 AN: 151958 Hom.: 17783 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.456 AC: 69385 AN: 152076 Hom.: 17817 Cov.: 33 AF XY: 0.459 AC XY: 34074 AN XY: 74302

African (AFR) AF: 0.686 AC: 28489 AN: 41520

American (AMR) AF: 0.394 AC: 6018 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1257 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3166 AN: 5164

South Asian (SAS) AF: 0.531 AC: 2556 AN: 4816

European-Finnish (FIN) AF: 0.331 AC: 3494 AN: 10544

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22935 AN: 67964

Other (OTH) AF: 0.450 AC: 950 AN: 2110

Alfa AF: 0.379 Hom.: 32523

Bravo AF: 0.467

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs669838; hg19: chr18-11994598;