rs915

Positions:

• chr8-81658155-C-T

Variant summary

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

The NM_005536.4(IMPA1):​c.*1196G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,852 control chromosomes in the GnomAD database, including 12,717 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 0.40 (12717 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IMPA1 NM_005536.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

Genes affected

IMPA1 (HGNC:6050): (inositol monophosphatase 1) This gene encodes an enzyme that dephosphorylates myo-inositol monophosphate to generate free myo-inositol, a precursor of phosphatidylinositol, and is therefore an important modulator of intracellular signal transduction via the production of the second messengers myoinositol 1,4,5-trisphosphate and diacylglycerol. This enzyme can also use myo-inositol-1,3-diphosphate, myo-inositol-1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. This enzyme shows magnesium-dependent phosphatase activity and is inhibited by therapeutic concentrations of lithium. Inhibition of inositol monophosphate hydroylosis and subsequent depletion of inositol for phosphatidylinositol synthesis may explain the anti-manic and anti-depressive effects of lithium administered to treat bipolar disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. A pseudogene of this gene is also present on chromosome 8q21.13. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPA1	NM_005536.4	c.*1196G>A		3_prime_UTR_variant	9/9	ENST00000256108.10	NP_005527.1
IMPA1	NM_001144878.2	c.*1196G>A		3_prime_UTR_variant	10/10		NP_001138350.1
IMPA1	NM_001144879.2	c.*1324G>A		3_prime_UTR_variant	8/8		NP_001138351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPA1	ENST00000256108	c.*1196G>A		3_prime_UTR_variant	9/9	1	NM_005536.4	ENSP00000256108.5

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60752 AN: 151736 Hom.: 12689 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.378

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.401 AC: 60840 AN: 151852 Hom.: 12717 Cov.: 32 AF XY: 0.402 AC XY: 29840 AN XY: 74212

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.380

Alfa AF: 0.384 Hom.: 2460

Bravo AF: 0.402

Asia WGS AF: 0.489 AC: 1700 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.098
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs915; hg19: chr8-82570390;