4-142176930-T-C

Variant names:

• chr4-142176930-T-C
• rs2636683
• NM_001101669.3:c.1182-3121A>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.1182-3121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,996 control chromosomes in the GnomAD database, including 32,215 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 0.65 (32215 hom., cov: 31)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 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.1182-3121A>G		intron	N/A	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.1182-3121A>G		intron	N/A	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.1182-3121A>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.1182-3121A>G		intron	N/A	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.1182-3121A>G		intron	N/A	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.1182-3121A>G		intron	N/A	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97993 AN: 151878 Hom.: 32201 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.645 AC: 98040 AN: 151996 Hom.: 32215 Cov.: 31 AF XY: 0.645 AC XY: 47918 AN XY: 74294

African (AFR) AF: 0.528 AC: 21887 AN: 41436

American (AMR) AF: 0.692 AC: 10563 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3468

East Asian (EAS) AF: 0.670 AC: 3462 AN: 5166

South Asian (SAS) AF: 0.592 AC: 2855 AN: 4822

European-Finnish (FIN) AF: 0.706 AC: 7465 AN: 10568

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47665 AN: 67954

Other (OTH) AF: 0.625 AC: 1320 AN: 2112

Alfa AF: 0.681 Hom.: 150791

Bravo AF: 0.640

Asia WGS AF: 0.613 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.81
PhyloP100		-0.24
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: rs2636683; hg19: chr4-143098083;