chr4-142040777-A-C

Variant names:

• chr4-142040777-A-C
• rs10519621
• NM_001101669.3:c.2643-11863T>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.2643-11863T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,210 control chromosomes in the GnomAD database, including 1,527 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 0.10 (1527 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.2643-11863T>G		intron_variant	Intron 25 of 25	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.2643-11863T>G		intron_variant	Intron 25 of 25	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15880 AN: 152092 Hom.: 1522 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.105 AC: 15907 AN: 152210 Hom.: 1527 Cov.: 32 AF XY: 0.100 AC XY: 7447 AN XY: 74426

African (AFR) AF: 0.256 AC: 10616 AN: 41494

American (AMR) AF: 0.0640 AC: 978 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4828

European-Finnish (FIN) AF: 0.0406 AC: 431 AN: 10604

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0490 AC: 3333 AN: 68016

Other (OTH) AF: 0.104 AC: 220 AN: 2116

Alfa AF: 0.137 Hom.: 840

Bravo AF: 0.115

Asia WGS AF: 0.0210 AC: 73 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.79
PhyloP100		0.61
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: rs10519621; hg19: chr4-142961930;