rs77389579

Variant names:

• chr4-142617358-G-T
• rs77389579
• NM_001101669.3:c.-191+108481C>A

Variant summary

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

The NM_001101669.3(INPP4B):​c.-191+108481C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 152,166 control chromosomes in the GnomAD database, including 59 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 0.025 (59 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• 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]

ENSG00000249806 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0533 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.-191+108481C>A		intron	N/A	NP_001095139.1
	INPP4B	NM_001331040.1		c.-191+108481C>A		intron	N/A	NP_001317969.1
	INPP4B	NM_001385335.1		c.-190-154632C>A		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.-191+108481C>A		intron	N/A	ENSP00000262992.4
	INPP4B	ENST00000513000.5	TSL:1	c.-290+108481C>A		intron	N/A	ENSP00000425487.1
	INPP4B	ENST00000509777.5	TSL:5	c.-191+108481C>A		intron	N/A	ENSP00000422793.1

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3772 AN: 152048 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.00924

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0248 AC: 3774 AN: 152166 Hom.: 59 Cov.: 32 AF XY: 0.0243 AC XY: 1804 AN XY: 74380

African (AFR) AF: 0.0159 AC: 662 AN: 41528

American (AMR) AF: 0.0190 AC: 290 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.0163 AC: 84 AN: 5150

South Asian (SAS) AF: 0.0590 AC: 284 AN: 4816

European-Finnish (FIN) AF: 0.00924 AC: 98 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1896 AN: 68010

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0275 Hom.: 23

Bravo AF: 0.0245

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.40
PhyloP100		-0.18
Mutation Taster		=100/0	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: rs77389579; hg19: chr4-143538511;