4-142308481-A-G

Variant names:

• chr4-142308481-A-G
• rs1907107
• NM_001101669.3:c.424-2944T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101669.3(INPP4B):​c.424-2944T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,768 control chromosomes in the GnomAD database, including 12,460 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 0.38 (12460 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101669.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	NM_001101669.3	MANE Select	c.424-2944T>C		intron	N/A	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.424-2944T>C		intron	N/A	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.424-2944T>C		intron	N/A	NP_001372264.1	E7EQN9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	ENST00000262992.9	TSL:5 MANE Select	c.424-2944T>C		intron	N/A	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.424-2944T>C		intron	N/A	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.424-2944T>C		intron	N/A	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57505 AN: 151648 Hom.: 12456 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.379 AC: 57518 AN: 151768 Hom.: 12460 Cov.: 32 AF XY: 0.388 AC XY: 28755 AN XY: 74124

African (AFR) AF: 0.146 AC: 6065 AN: 41498

American (AMR) AF: 0.474 AC: 7223 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3121 AN: 5130

South Asian (SAS) AF: 0.512 AC: 2460 AN: 4808

European-Finnish (FIN) AF: 0.506 AC: 5303 AN: 10474

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30599 AN: 67828

Other (OTH) AF: 0.385 AC: 813 AN: 2110

Alfa AF: 0.419 Hom.: 32400

Bravo AF: 0.364

Asia WGS AF: 0.489 AC: 1695 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.39
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1907107;

hg19: chr4-143229634;