Variant rs140797474 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.1159+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,608,534 control chromosomes in the GnomAD database, including 498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 40 hom., cov: 34)

Exomes 𝑓: 0.021 ( 458 hom. )

Consequence

INPP5E
NM_019892.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.47

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=-1.01).

BP6

Variant 9-136433129-G-A is Benign according to our data. Variant chr9-136433129-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP5E	NM_019892.6 linkuse as main transcript	c.1159+26C>T		intron_variant		ENST00000371712.4	NP_063945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP5E	ENST00000371712.4 linkuse as main transcript	c.1159+26C>T		intron_variant		1	NM_019892.6	ENSP00000360777	P1	Q9NRR6-1
INPP5E	ENST00000676019.1 linkuse as main transcript	c.1057+26C>T		intron_variant				ENSP00000501984		Q9NRR6-2

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2485

AN:

151474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00524

Gnomad AMI

AF:

0.0287

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0810

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0274

GnomAD3 exomes

AF:

0.0184

AC:

4496

AN:

244508

Hom.:

AF XY:

0.0189

AC XY:

2521

AN XY:

133290

show subpopulations

Gnomad AFR exome

AF:

0.00568

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0800

Gnomad EAS exome

AF:

0.000605

Gnomad SAS exome

AF:

0.00805

Gnomad FIN exome

AF:

0.00307

Gnomad NFE exome

AF:

0.0228

Gnomad OTH exome

AF:

0.0281

GnomAD4 exome

AF:

0.0212

AC:

30908

AN:

1456942

Hom.:

458

Cov.:

AF XY:

0.0212

AC XY:

15387

AN XY:

724940

show subpopulations

Gnomad4 AFR exome

AF:

0.00545

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0801

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00827

Gnomad4 FIN exome

AF:

0.00379

Gnomad4 NFE exome

AF:

0.0226

Gnomad4 OTH exome

AF:

0.0247

GnomAD4 genome

AF:

0.0164

AC:

2484

AN:

151592

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1200

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.00522

Gnomad4 AMR

AF:

0.0245

Gnomad4 ASJ

AF:

0.0810

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0271

Alfa

AF:

0.0296

Hom.:

Bravo

AF:

0.0212

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

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

-1.0

CADD

Benign

0.028

DANN

Benign

0.69

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

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