rs11676357

Variant names:

• chr2-98491814-A-G
• rs11676357
• NM_001134225.2:c.-165-27150A>G

Variant summary

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

The NM_001134225.2(INPP4A):​c.-165-27150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,980 control chromosomes in the GnomAD database, including 17,929 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 0.48 (17929 hom., cov: 32)
• Consequence: INPP4A NM_001134225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 11 publications found

Genes affected

INPP4A (HGNC:6074): (inositol polyphosphate-4-phosphatase type I A) This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

INPP4A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4A	NM_001134225.2	c.-165-27150A>G		intron_variant	Intron 1 of 24	ENST00000409851.8	NP_001127697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4A	ENST00000409851.8	c.-165-27150A>G		intron_variant	Intron 1 of 24	1	NM_001134225.2	ENSP00000386777.4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73089 AN: 151862 Hom.: 17927 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.481 AC: 73119 AN: 151980 Hom.: 17929 Cov.: 32 AF XY: 0.475 AC XY: 35258 AN XY: 74274

African (AFR) AF: 0.527 AC: 21820 AN: 41438

American (AMR) AF: 0.471 AC: 7202 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1393 AN: 5174

South Asian (SAS) AF: 0.480 AC: 2305 AN: 4802

European-Finnish (FIN) AF: 0.372 AC: 3928 AN: 10562

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33180 AN: 67944

Other (OTH) AF: 0.481 AC: 1012 AN: 2102

Alfa AF: 0.487 Hom.: 10962

Bravo AF: 0.488

Asia WGS AF: 0.399 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		0.35
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: rs11676357; hg19: chr2-99108277;