4-142303594-C-T

Variant names:

• chr4-142303594-C-T
• rs10519638
• NM_001101669.3:c.503+1864G>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.503+1864G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 152,030 control chromosomes in the GnomAD database, including 723 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 0.084 (723 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.503+1864G>A		intron_variant	Intron 9 of 25	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.503+1864G>A		intron_variant	Intron 9 of 25	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12794 AN: 151912 Hom.: 724 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0814

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

GnomAD4 genome AF: 0.0841 AC: 12792 AN: 152030 Hom.: 723 Cov.: 32 AF XY: 0.0840 AC XY: 6241 AN XY: 74306

African (AFR) AF: 0.146 AC: 6059 AN: 41492

American (AMR) AF: 0.0799 AC: 1218 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3464

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5174

South Asian (SAS) AF: 0.0637 AC: 307 AN: 4822

European-Finnish (FIN) AF: 0.0577 AC: 610 AN: 10570

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0532 AC: 3612 AN: 67946

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0654 Hom.: 242

Bravo AF: 0.0893

Asia WGS AF: 0.0490 AC: 170 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-0.38
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: rs10519638; hg19: chr4-143224747;