Variant rs34302850 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 ENST00000371712.4(INPP5E):c.1280-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,418,354 control chromosomes in the GnomAD database, including 57,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.25 ( 5217 hom., cov: 33)

Exomes 𝑓: 0.28 ( 52714 hom. )

Consequence

INPP5E
ENST00000371712.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.72

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-136432612-A-G is Benign according to our data. Variant chr9-136432612-A-G is described in ClinVar as [Benign]. Clinvar id is 261192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 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.1280-26T>C		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.1280-26T>C		intron_variant		1	NM_019892.6	ENSP00000360777	P1	Q9NRR6-1
INPP5E	ENST00000676019.1 linkuse as main transcript	c.1178-26T>C		intron_variant				ENSP00000501984		Q9NRR6-2

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38630

AN:

151922

Hom.:

5216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.0557

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.275

GnomAD3 exomes

AF:

0.256

AC:

39039

AN:

152248

Hom.:

5617

AF XY:

0.250

AC XY:

20161

AN XY:

80488

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.0424

Gnomad SAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.282

AC:

356609

AN:

1266314

Hom.:

52714

Cov.:

AF XY:

0.278

AC XY:

175651

AN XY:

630720

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.0888

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.254

AC:

38649

AN:

152040

Hom.:

5217

Cov.:

AF XY:

0.250

AC XY:

18613

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.0552

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.291

Hom.:

1803

Bravo

AF:

0.253

Asia WGS

AF:

0.147

AC:

511

AN:

3476

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

-0.90

CADD

Benign

1.0

DANN

Benign

0.31

BranchPoint Hunter

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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