4-142352558-G-A

Variant names:

• chr4-142352558-G-A
• rs1497393
• NM_001101669.3:c.373-37796C>T

Variant summary

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

The NM_001101669.3(INPP4B):​c.373-37796C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,296 control chromosomes in the GnomAD database, including 12,365 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 0.40 (12365 hom., cov: 31)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	NM_001101669.3	MANE Select	c.373-37796C>T		intron	N/A	NP_001095139.1
	INPP4B	NM_001331040.1		c.373-37796C>T		intron	N/A	NP_001317969.1
	INPP4B	NM_001385335.1		c.373-37796C>T		intron	N/A	NP_001372264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	ENST00000262992.9	TSL:5 MANE Select	c.373-37796C>T		intron	N/A	ENSP00000262992.4
	INPP4B	ENST00000508116.5	TSL:1	c.373-37796C>T		intron	N/A	ENSP00000423954.1
	INPP4B	ENST00000513000.5	TSL:1	c.373-37796C>T		intron	N/A	ENSP00000425487.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60334 AN: 151184 Hom.: 12359 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.399 AC: 60356 AN: 151296 Hom.: 12365 Cov.: 31 AF XY: 0.404 AC XY: 29853 AN XY: 73860

African (AFR) AF: 0.422 AC: 17445 AN: 41302

American (AMR) AF: 0.431 AC: 6522 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3265 AN: 5098

South Asian (SAS) AF: 0.393 AC: 1886 AN: 4802

European-Finnish (FIN) AF: 0.458 AC: 4771 AN: 10428

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24093 AN: 67750

Other (OTH) AF: 0.390 AC: 820 AN: 2104

Alfa AF: 0.368 Hom.: 5790

Bravo AF: 0.398

Asia WGS AF: 0.465 AC: 1614 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.20
PhyloP100		-0.42
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: rs1497393; hg19: chr4-143273711;