4-142128827-T-C

Position:

• chr4-142128827-T-C

Variant summary

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

The NM_001101669.3(INPP4B):​c.1721-4067A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,116 control chromosomes in the GnomAD database, including 1,704 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 0.14 (1704 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08

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]

INPP4B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.1721-4067A>G		intron_variant		ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.1721-4067A>G		intron_variant		5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21443 AN: 151998 Hom.: 1702 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.141 AC: 21450 AN: 152116 Hom.: 1704 Cov.: 32 AF XY: 0.139 AC XY: 10325 AN XY: 74368

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.149

Alfa AF: 0.126 Hom.: 2150

Bravo AF: 0.150

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.034
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3775652; hg19: chr4-143049980;