rs1497393

Positions:

• chr4-142352558-G-A
• chr4-142352558-G-C

Variant summary

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

The NM_001101669.3(INPP4B):​c.373-37796C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,296 control chromosomes in the GnomAD database, including 12,365 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 0.40 (12365 hom., cov: 31)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

Genes affected

INPP4B (HGNC:6075): (inositol polyphosphate-4-phosphatase type II B) INPP4B encodes the inositol polyphosphate 4-phosphatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. There is limited data to suggest that the human type II enzyme is subject to alternative splicing, as has been established for the type I enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP4B	NM_001101669.3	c.373-37796C>T		intron_variant		ENST00000262992.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP4B	ENST00000262992.9	c.373-37796C>T		intron_variant		5	NM_001101669.3	P3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60334 AN: 151184 Hom.: 12359 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.399 AC: 60356 AN: 151296 Hom.: 12365 Cov.: 31 AF XY: 0.404 AC XY: 29853 AN XY: 73860

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.390

Alfa AF: 0.369 Hom.: 5285

Bravo AF: 0.398

Asia WGS AF: 0.465 AC: 1614 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.20

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: rs1497393; hg19: chr4-143273711;