4-142375336-C-T

Variant names:

• chr4-142375336-C-T
• rs4956319
• NM_001101669.3:c.372+27602G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001101669.3(INPP4B):​c.372+27602G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 150,006 control chromosomes in the GnomAD database, including 83 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 0.028 (83 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.028 (4205/150006) while in subpopulation NFE AF= 0.044 (2968/67496). AF 95% confidence interval is 0.0427. There are 83 homozygotes in gnomad4. There are 1986 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 83 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.372+27602G>A		intron_variant	Intron 7 of 25	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.372+27602G>A		intron_variant	Intron 7 of 25	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4201 AN: 149890 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00768

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00824

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0439

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0280 AC: 4205 AN: 150006 Hom.: 83 Cov.: 32 AF XY: 0.0272 AC XY: 1986 AN XY: 73142

Gnomad4 AFR AF: 0.00769

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.0261

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00845

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0440

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0394 Hom.: 168

Bravo AF: 0.0268

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.69

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: rs4956319; hg19: chr4-143296489;