chr4-142375336-C-T

Variant names:

• chr4-142375336-C-T
• rs4956319
• NM_001101669.3:c.372+27602G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001101669.3(INPP4B):​c.372+27602G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 150,006 control chromosomes in the GnomAD database, including 83 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 0.028 (83 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 0 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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.028 (4205/150006) while in subpopulation NFE AF = 0.044 (2968/67496). AF 95% confidence interval is 0.0427. There are 83 homozygotes in GnomAd4. There are 1986 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 83 AR gene

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.372+27602G>A		intron	N/A	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.372+27602G>A		intron	N/A	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.372+27602G>A		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.372+27602G>A		intron	N/A	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.372+27602G>A		intron	N/A	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.372+27602G>A		intron	N/A	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4201 AN: 149890 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00768

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00824

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0439

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0280 AC: 4205 AN: 150006 Hom.: 83 Cov.: 32 AF XY: 0.0272 AC XY: 1986 AN XY: 73142

African (AFR) AF: 0.00769 AC: 314 AN: 40850

American (AMR) AF: 0.0266 AC: 398 AN: 14952

Ashkenazi Jewish (ASJ) AF: 0.0261 AC: 90 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5028

South Asian (SAS) AF: 0.00845 AC: 40 AN: 4732

European-Finnish (FIN) AF: 0.0298 AC: 305 AN: 10218

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.0440 AC: 2968 AN: 67496

Other (OTH) AF: 0.0322 AC: 67 AN: 2082

Alfa AF: 0.0382 Hom.: 207

Bravo AF: 0.0268

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		0.091
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: rs4956319; hg19: chr4-143296489;