4-142197220-T-C

Variant names:

• chr4-142197220-T-C
• rs2627821
• NM_001101669.3:c.1073-4025A>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.1073-4025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 151,632 control chromosomes in the GnomAD database, including 58,979 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 0.88 (58979 hom., cov: 28)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 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.1073-4025A>G		intron	N/A	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.1073-4025A>G		intron	N/A	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.1073-4025A>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.1073-4025A>G		intron	N/A	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.1073-4025A>G		intron	N/A	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.1073-4025A>G		intron	N/A	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 132735 AN: 151514 Hom.: 58938 Cov.: 28

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.817

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.876 AC: 132828 AN: 151632 Hom.: 58979 Cov.: 28 AF XY: 0.878 AC XY: 65037 AN XY: 74056

African (AFR) AF: 0.715 AC: 29487 AN: 41248

American (AMR) AF: 0.903 AC: 13759 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2895 AN: 3470

East Asian (EAS) AF: 0.957 AC: 4921 AN: 5142

South Asian (SAS) AF: 0.937 AC: 4503 AN: 4806

European-Finnish (FIN) AF: 0.954 AC: 9990 AN: 10470

Middle Eastern (MID) AF: 0.821 AC: 238 AN: 290

European-Non Finnish (NFE) AF: 0.946 AC: 64298 AN: 67948

Other (OTH) AF: 0.897 AC: 1887 AN: 2104

Alfa AF: 0.870 Hom.: 8741

Bravo AF: 0.863

Asia WGS AF: 0.930 AC: 3235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.2
DANN	Benign	0.77
PhyloP100		-0.34
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: rs2627821; hg19: chr4-143118373;