2-190368449-G-A

Variant names:

• chr2-190368449-G-A
• rs909270
• NM_001128928.2:c.467-654G>A

Variant summary

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

The NM_001128928.2(INPP1):​c.467-654G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,398 control chromosomes in the GnomAD database, including 31,087 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 0.64 (31087 hom., cov: 32)
• Consequence: INPP1 NM_001128928.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128928.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP1	NM_001128928.2	MANE Select	c.467-654G>A		intron	N/A	NP_001122400.1
	INPP1	NM_002194.4		c.467-654G>A		intron	N/A	NP_002185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP1	ENST00000392329.7	TSL:5 MANE Select	c.467-654G>A		intron	N/A	ENSP00000376142.2
	INPP1	ENST00000322522.8	TSL:1	c.467-654G>A		intron	N/A	ENSP00000325423.4
	INPP1	ENST00000431594.5	TSL:3	c.467-654G>A		intron	N/A	ENSP00000409786.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96137 AN: 151278 Hom.: 31042 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.636 AC: 96237 AN: 151398 Hom.: 31087 Cov.: 32 AF XY: 0.637 AC XY: 47118 AN XY: 74004

African (AFR) AF: 0.724 AC: 29630 AN: 40940

American (AMR) AF: 0.741 AC: 11297 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3468

East Asian (EAS) AF: 0.760 AC: 3928 AN: 5168

South Asian (SAS) AF: 0.510 AC: 2454 AN: 4814

European-Finnish (FIN) AF: 0.548 AC: 5764 AN: 10514

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38989 AN: 67954

Other (OTH) AF: 0.648 AC: 1356 AN: 2094

Alfa AF: 0.598 Hom.: 50671

Bravo AF: 0.654

Asia WGS AF: 0.605 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.11
PhyloP100		0.39
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: rs909270; hg19: chr2-191233175;