rs12617721

chr2-98467429-A-Cchr2-98467429-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134225.2(INPP4A):c.-166+22344A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,966 control chromosomes in the GnomAD database, including 5,790 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 0.28 (5790 hom., cov: 32)
• Consequence: INPP4A NM_001134225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP4A	NM_001134225.2	c.-166+22344A>C		intron_variant		ENST00000409851.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP4A	ENST00000409851.8	c.-166+22344A>C		intron_variant		1	NM_001134225.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41767 AN: 151848 Hom.: 5789 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.275 AC: 41796 AN: 151966 Hom.: 5790 Cov.: 32 AF XY: 0.273 AC XY: 20282 AN XY: 74308

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.317

Alfa AF: 0.274 Hom.: 994

Bravo AF: 0.281

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.1
Dann	Benign	0.50

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: rs12617721; hg19: chr2-99083892;