4-142086248-G-C

Variant names:

• chr4-142086248-G-C
• rs143281990
• NM_001101669.3:c.2383C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001101669.3(INPP4B):​c.2383C>G​(p.His795Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H795Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: INPP4B NM_001101669.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11596912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.2383C>G	p.His795Asp	missense_variant	Exon 24 of 26	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.2383C>G	p.His795Asp	missense_variant	Exon 24 of 26	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T;T;T;T;T;.;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	.;T;.;T;T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	N;N;N;.;.;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.83	T;T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;.;.;T
Polyphen		0.011	B;B;B;.;.;.;.
Vest4		0.50
MutPred		0.21		Gain of disorder (P = 0.0486);Gain of disorder (P = 0.0486);Gain of disorder (P = 0.0486);Gain of disorder (P = 0.0486);.;Gain of disorder (P = 0.0486);.;
MVP		0.093
MPC		0.28
ClinPred		0.54	D
GERP RS		4.0
Varity_R		0.15
gMVP		0.43
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs143281990; hg19: chr4-143007401;