Variant chr8-81676288-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000256108.10(IMPA1):c.303-9T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,218,780 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 2 hom. )

Consequence

IMPA1
ENST00000256108.10 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.2507

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.103

Variant links:

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]

IMPA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-81676288-A-T is Benign according to our data. Variant chr8-81676288-A-T is described in ClinVar as [Benign]. Clinvar id is 716533.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
IMPA1	NM_005536.4 linkuse as main transcript	c.303-9T>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000256108.10	NP_005527.1
IMPA1	NM_001144878.2 linkuse as main transcript	c.480-9T>A	splice_polypyrimidine_tract_variant, intron_variant		NP_001138350.1
IMPA1	NM_001144879.2 linkuse as main transcript	c.303-9T>A	splice_polypyrimidine_tract_variant, intron_variant		NP_001138351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPA1	ENST00000256108.10 linkuse as main transcript	c.303-9T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005536.4	ENSP00000256108	P1	P29218-1

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

291

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000759

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00182

AC:

296

AN:

162784

Hom.:

AF XY:

0.00197

AC XY:

178

AN XY:

90300

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.000164

Gnomad EAS exome

AF:

0.00161

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00243

Gnomad OTH exome

AF:

0.00208

GnomAD4 exome

AF:

0.00172

AC:

1830

AN:

1066734

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

930

AN XY:

538344

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.000986

Gnomad4 ASJ exome

AF:

0.000102

Gnomad4 EAS exome

AF:

0.000979

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.00119

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.00170

GnomAD4 genome

AF:

0.00191

AC:

291

AN:

152046

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000759

Gnomad4 NFE

AF:

0.00297

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.00181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0060

DANN

Benign

0.39

BranchPoint Hunter

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.25

dbscSNV1_RF

Benign

0.42

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: -9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over