rs10519659

Variant names:

• chr4-142413904-G-C
• rs10519659
• NM_001101669.3:c.137-8580C>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.137-8580C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 152,120 control chromosomes in the GnomAD database, including 140 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 0.037 (140 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.137-8580C>G		intron_variant	Intron 5 of 25	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.137-8580C>G		intron_variant	Intron 5 of 25	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5565 AN: 152002 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.00903

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.0355

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0456

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

GnomAD4 genome AF: 0.0366 AC: 5571 AN: 152120 Hom.: 140 Cov.: 32 AF XY: 0.0367 AC XY: 2729 AN XY: 74346

African (AFR) AF: 0.00903 AC: 375 AN: 41538

American (AMR) AF: 0.0728 AC: 1111 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3470

East Asian (EAS) AF: 0.0531 AC: 274 AN: 5160

South Asian (SAS) AF: 0.0355 AC: 171 AN: 4816

European-Finnish (FIN) AF: 0.0308 AC: 325 AN: 10562

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3076 AN: 67994

Other (OTH) AF: 0.0475 AC: 100 AN: 2106

Alfa AF: 0.0411 Hom.: 16

Bravo AF: 0.0394

Asia WGS AF: 0.0770 AC: 266 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.79
PhyloP100		0.030
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: rs10519659; hg19: chr4-143335057;