4-142054920-A-G

Variant names:

• chr4-142054920-A-G
• rs2667100
• NM_001101669.3:c.2643-26006T>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.2643-26006T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 151,896 control chromosomes in the GnomAD database, including 52,469 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 0.81 (52469 hom., cov: 31)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 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.2643-26006T>C		intron	N/A	NP_001095139.1
	INPP4B	NM_001331040.1		c.2643-24618T>C		intron	N/A	NP_001317969.1
	INPP4B	NM_001385335.1		c.2643-24618T>C		intron	N/A	NP_001372264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	ENST00000262992.9	TSL:5 MANE Select	c.2643-26006T>C		intron	N/A	ENSP00000262992.4
	INPP4B	ENST00000508116.5	TSL:1	c.2643-26006T>C		intron	N/A	ENSP00000423954.1
	INPP4B	ENST00000513000.5	TSL:1	c.2643-26006T>C		intron	N/A	ENSP00000425487.1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123593 AN: 151776 Hom.: 52457 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.833

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.814 AC: 123642 AN: 151896 Hom.: 52469 Cov.: 31 AF XY: 0.818 AC XY: 60757 AN XY: 74266

African (AFR) AF: 0.548 AC: 22666 AN: 41364

American (AMR) AF: 0.882 AC: 13429 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2942 AN: 3470

East Asian (EAS) AF: 0.919 AC: 4735 AN: 5154

South Asian (SAS) AF: 0.897 AC: 4318 AN: 4812

European-Finnish (FIN) AF: 0.950 AC: 10059 AN: 10594

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.922 AC: 62694 AN: 67964

Other (OTH) AF: 0.828 AC: 1742 AN: 2104

Alfa AF: 0.887 Hom.: 102908

Bravo AF: 0.798

Asia WGS AF: 0.871 AC: 3026 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.44
PhyloP100		-0.90
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

Other links and lift over

dbSNP: rs2667100; hg19: chr4-142976073;