2-98544045-GCACACA-GCA

Position:

• chr2-98544045-GCACACA-GCA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001134225.2(INPP4A):​c.949+54_949+57delACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,427,044 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: INPP4A NM_001134225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP4A	NM_001134225.2	c.949+54_949+57delACAC		intron_variant		ENST00000409851.8	NP_001127697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP4A	ENST00000409851.8	c.949+54_949+57delACAC		intron_variant		1	NM_001134225.2	ENSP00000386777.4

Frequencies

GnomAD3 genomes AF: 0.0000598 AC: 9 AN: 150402 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000982

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00216 AC: 233 AN: 107972 Hom.: 0 AF XY: 0.00223 AC XY: 127 AN XY: 56910

Gnomad AFR exome AF: 0.000674

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00409

Gnomad EAS exome AF: 0.00276

Gnomad SAS exome AF: 0.00254

Gnomad FIN exome AF: 0.00294

Gnomad NFE exome AF: 0.00178

Gnomad OTH exome AF: 0.00220

GnomAD4 exome AF: 0.00117 AC: 1489 AN: 1276532 Hom.: 0 AF XY: 0.00118 AC XY: 739 AN XY: 628870

Gnomad4 AFR exome AF: 0.000854

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00203

Gnomad4 EAS exome AF: 0.00124

Gnomad4 SAS exome AF: 0.00175

Gnomad4 FIN exome AF: 0.000830

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.00115

GnomAD4 genome AF: 0.0000598 AC: 9 AN: 150512 Hom.: 0 Cov.: 24 AF XY: 0.0000680 AC XY: 5 AN XY: 73498

Gnomad4 AFR AF: 0.0000979

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3217304; hg19: chr2-99160508;