Variant rs4451431 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019892.6(INPP5E):c.1802+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,548,680 control chromosomes in the GnomAD database, including 18,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1962 hom., cov: 33)

Exomes 𝑓: 0.15 ( 16312 hom. )

Consequence

INPP5E
NM_019892.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.126

Variant links:

Genes affected

INPP5E (HGNC:21474): (inositol polyphosphate-5-phosphatase E) The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. Studies of the mouse counterpart suggest that this protein may hydrolyze phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,5-bisphosphate on the cytoplasmic Golgi membrane and thereby regulate Golgi-vesicular trafficking. Mutations in this gene cause Joubert syndrome; a clinically and genetically heterogenous group of disorders characterized by midbrain-hindbrain malformation and various associated ciliopathies that include retinal dystrophy, nephronophthisis, liver fibrosis and polydactyly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

INPP5E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 9-136430228-C-T is Benign according to our data. Variant chr9-136430228-C-T is described in ClinVar as [Benign]. Clinvar id is 261200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
INPP5E	NM_019892.6 link	c.1802+49G>A	intron_variant	ENST00000371712.4	NP_063945.2	Q9NRR6-1
INPP5E	NM_001318502.2 link	c.1799+49G>A	intron_variant		NP_001305431.1	Q9NRR6
INPP5E	XM_017014926.2 link	c.1802+49G>A	intron_variant		XP_016870415.1
INPP5E	XM_047423603.1 link	c.1799+49G>A	intron_variant		XP_047279559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP5E	ENST00000371712.4 link	c.1802+49G>A		intron_variant		1	NM_019892.6	ENSP00000360777.3		Q9NRR6-1
INPP5E	ENST00000676019.1 link	c.1700+49G>A		intron_variant				ENSP00000501984.1		Q9NRR6-2

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23435

AN:

152092

Hom.:

1948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0732

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.161

AC:

24945

AN:

154834

Hom.:

2324

AF XY:

0.156

AC XY:

12746

AN XY:

81512

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.0688

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.149

AC:

208116

AN:

1396470

Hom.:

16312

Cov.:

AF XY:

0.149

AC XY:

102456

AN XY:

688700

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.0736

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.154

AC:

23488

AN:

152210

Hom.:

1962

Cov.:

AF XY:

0.152

AC XY:

11310

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0732

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.144

Hom.:

423

Bravo

AF:

0.169

Asia WGS

AF:

0.166

AC:

579

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.7

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over