rs13104269

Variant names:

• chr4-142417552-A-G
• rs13104269
• NM_001101669.3:c.136+11621T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101669.3(INPP4B):​c.136+11621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,212 control chromosomes in the GnomAD database, including 670 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 0.091 (670 hom., cov: 32)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.136+11621T>C		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.136+11621T>C		intron_variant	Intron 5 of 25	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13882 AN: 152092 Hom.: 668 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0984

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

GnomAD4 genome AF: 0.0913 AC: 13899 AN: 152212 Hom.: 670 Cov.: 32 AF XY: 0.0940 AC XY: 6997 AN XY: 74418

African (AFR) AF: 0.113 AC: 4694 AN: 41532

American (AMR) AF: 0.0969 AC: 1480 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3470

East Asian (EAS) AF: 0.0721 AC: 373 AN: 5174

South Asian (SAS) AF: 0.100 AC: 483 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1307 AN: 10608

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.0688 AC: 4679 AN: 68012

Other (OTH) AF: 0.0974 AC: 206 AN: 2116

Alfa AF: 0.0799 Hom.: 1083

Bravo AF: 0.0923

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.79
PhyloP100		0.40
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: rs13104269; hg19: chr4-143338705;