2-190360201-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001128928.2(INPP1):c.99C>T(p.Ile33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,613,938 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (105 hom.)
• Consequence: INPP1 NM_001128928.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.59

Genes affected

INPP1 (HGNC:6071): (inositol polyphosphate-1-phosphatase) This gene encodes the enzyme inositol polyphosphate-1-phosphatase, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 1 of the inositol ring from the polyphosphates inositol 1,4-bisphosphate and inositol 1,3,4-trisphophosphate. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-190360201-C-T is Benign according to our data. Variant chr2-190360201-C-T is described in ClinVar as [Benign]. Clinvar id is 773848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP1	NM_001128928.2	c.99C>T	p.Ile33=	synonymous_variant	3/7	ENST00000392329.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP1	ENST00000392329.7	c.99C>T	p.Ile33=	synonymous_variant	3/7	5	NM_001128928.2	P1

Frequencies

GnomAD3 genomes AF: 0.00630 AC: 957 AN: 151978 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00911

GnomAD3 exomes AF: 0.0113 AC: 2829 AN: 251408 Hom.: 88 AF XY: 0.00925 AC XY: 1257 AN XY: 135888

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.0560

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0431

Gnomad SAS exome AF: 0.000947

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00782

GnomAD4 exome AF: 0.00293 AC: 4281 AN: 1461842 Hom.: 105 Cov.: 30 AF XY: 0.00266 AC XY: 1934 AN XY: 727228

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0365

Gnomad4 SAS exome AF: 0.000939

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000638

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.00633 AC: 963 AN: 152096 Hom.: 20 Cov.: 33 AF XY: 0.00734 AC XY: 546 AN XY: 74352

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0461

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.00343 Hom.: 13

Bravo AF: 0.00963

Asia WGS AF: 0.0260 AC: 91 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	5.5
Dann	Benign	0.87

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: rs2067404; hg19: chr2-191224927;