rs3775652

Variant names:

• chr4-142128827-T-C
• rs3775652
• NM_001101669.3:c.1721-4067A>G

Variant summary

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

The NM_001101669.3(INPP4B):​c.1721-4067A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,116 control chromosomes in the GnomAD database, including 1,704 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 0.14 (1704 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• Publications: 7 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 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.1721-4067A>G		intron	N/A	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.1721-4067A>G		intron	N/A	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.1721-4067A>G		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.1721-4067A>G		intron	N/A	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.1721-4067A>G		intron	N/A	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.1721-4067A>G		intron	N/A	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21443 AN: 151998 Hom.: 1702 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.141 AC: 21450 AN: 152116 Hom.: 1704 Cov.: 32 AF XY: 0.139 AC XY: 10325 AN XY: 74368

African (AFR) AF: 0.183 AC: 7571 AN: 41456

American (AMR) AF: 0.139 AC: 2132 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3472

East Asian (EAS) AF: 0.241 AC: 1242 AN: 5152

South Asian (SAS) AF: 0.0880 AC: 425 AN: 4828

European-Finnish (FIN) AF: 0.112 AC: 1184 AN: 10602

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7579 AN: 67998

Other (OTH) AF: 0.149 AC: 315 AN: 2110

Alfa AF: 0.126 Hom.: 4931

Bravo AF: 0.150

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.034
DANN	Benign	0.63
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3775652; hg19: chr4-143049980;