2-98544045-GCACACACA-GCACACA

Variant names:

• chr2-98544045-GCA-G
• rs3217304
• NM_001134225.2:c.949+56_949+57delAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001134225.2(INPP4A):​c.949+56_949+57delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,380,998 control chromosomes in the GnomAD database, including 32,293 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4730 hom., cov: 24)
  • Exomes 𝑓: 0.25 (27563 hom.)
• Consequence: INPP4A NM_001134225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 4 publications found

Genes affected

INPP4A (HGNC:6074): (inositol polyphosphate-4-phosphatase type I A) This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

INPP4A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134225.2. 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
	INPP4A	NM_001134225.2	MANE Select	c.949+56_949+57delAC		intron	N/A	NP_001127697.1	Q96PE3-3
	INPP4A	NM_001351425.2	MANE Plus Clinical	c.949+56_949+57delAC		intron	N/A	NP_001338354.1	A0ABB0MUY6
	INPP4A	NM_001134224.2		c.949+56_949+57delAC		intron	N/A	NP_001127696.1	Q96PE3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4A	ENST00000409851.8	TSL:1 MANE Select	c.949+39_949+40delCA		intron	N/A	ENSP00000386777.4	Q96PE3-3
	INPP4A	ENST00000715854.1	MANE Plus Clinical	c.949+39_949+40delCA		intron	N/A	ENSP00000520526.1	A0ABB0MUY6
	INPP4A	ENST00000523221.2	TSL:1	c.949+39_949+40delCA		intron	N/A	ENSP00000427722.1	Q96PE3-1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 37826 AN: 150268 Hom.: 4727 Cov.: 24

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.320 AC: 34509 AN: 107972 AF XY: 0.323

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.331

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.254 AC: 312148 AN: 1230620 Hom.: 27563 AF XY: 0.255 AC XY: 154833 AN XY: 606288

African (AFR) AF: 0.238 AC: 6619 AN: 27852

American (AMR) AF: 0.297 AC: 9485 AN: 31942

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 7454 AN: 21712

East Asian (EAS) AF: 0.298 AC: 9136 AN: 30654

South Asian (SAS) AF: 0.274 AC: 19340 AN: 70560

European-Finnish (FIN) AF: 0.214 AC: 8601 AN: 40246

Middle Eastern (MID) AF: 0.315 AC: 1546 AN: 4906

European-Non Finnish (NFE) AF: 0.248 AC: 236230 AN: 952212

Other (OTH) AF: 0.272 AC: 13737 AN: 50536

GnomAD4 genome AF: 0.252 AC: 37860 AN: 150378 Hom.: 4730 Cov.: 24 AF XY: 0.250 AC XY: 18386 AN XY: 73410

African (AFR) AF: 0.234 AC: 9540 AN: 40794

American (AMR) AF: 0.277 AC: 4199 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1166 AN: 3452

East Asian (EAS) AF: 0.295 AC: 1515 AN: 5132

South Asian (SAS) AF: 0.294 AC: 1399 AN: 4754

European-Finnish (FIN) AF: 0.200 AC: 2065 AN: 10304

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17114 AN: 67522

Other (OTH) AF: 0.291 AC: 607 AN: 2084

Alfa AF: 0.188 Hom.: 390

Bravo AF: 0.256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
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: rs3217304; hg19: chr2-99160508;