9-136433147-G-GCGCCCACCCCTCCAGCCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_019892.6(INPP5E):​c.1159+7_1159+8insTGGCTGGAGGGGTGGGCG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 147,718 control chromosomes in the GnomAD database, including 5,144 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5144 hom., cov: 28)
Exomes 𝑓: 0.29 ( 63852 hom. )
Failed GnomAD Quality Control

Consequence

INPP5E
NM_019892.6 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.695
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 9-136433147-G-GCGCCCACCCCTCCAGCCA is Benign according to our data. Variant chr9-136433147-G-GCGCCCACCCCTCCAGCCA is described in ClinVar as [Likely_benign]. Clinvar id is 215526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INPP5ENM_019892.6 linkc.1159+7_1159+8insTGGCTGGAGGGGTGGGCG splice_region_variant, intron_variant Intron 4 of 9 ENST00000371712.4 NP_063945.2 Q9NRR6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INPP5EENST00000371712.4 linkc.1159+7_1159+8insTGGCTGGAGGGGTGGGCG splice_region_variant, intron_variant Intron 4 of 9 1 NM_019892.6 ENSP00000360777.3 Q9NRR6-1
INPP5EENST00000676019.1 linkc.1057+7_1057+8insTGGCTGGAGGGGTGGGCG splice_region_variant, intron_variant Intron 4 of 9 ENSP00000501984.1 Q9NRR6-2

Frequencies

GnomAD3 genomes
AF:
0.258
AC:
38034
AN:
147600
Hom.:
5142
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.196
Gnomad AMI
AF:
0.287
Gnomad AMR
AF:
0.286
Gnomad ASJ
AF:
0.247
Gnomad EAS
AF:
0.0447
Gnomad SAS
AF:
0.164
Gnomad FIN
AF:
0.277
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.307
Gnomad OTH
AF:
0.263
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.289
AC:
417440
AN:
1443622
Hom.:
63852
Cov.:
53
AF XY:
0.285
AC XY:
204963
AN XY:
718522
show subpopulations
Gnomad4 AFR exome
AF:
0.187
Gnomad4 AMR exome
AF:
0.283
Gnomad4 ASJ exome
AF:
0.253
Gnomad4 EAS exome
AF:
0.0762
Gnomad4 SAS exome
AF:
0.170
Gnomad4 FIN exome
AF:
0.276
Gnomad4 NFE exome
AF:
0.313
Gnomad4 OTH exome
AF:
0.267
GnomAD4 genome
AF:
0.258
AC:
38065
AN:
147718
Hom.:
5144
Cov.:
28
AF XY:
0.252
AC XY:
18158
AN XY:
72098
show subpopulations
Gnomad4 AFR
AF:
0.196
Gnomad4 AMR
AF:
0.286
Gnomad4 ASJ
AF:
0.247
Gnomad4 EAS
AF:
0.0446
Gnomad4 SAS
AF:
0.163
Gnomad4 FIN
AF:
0.277
Gnomad4 NFE
AF:
0.307
Gnomad4 OTH
AF:
0.263
Alfa
AF:
0.209
Hom.:
959

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Oct 24, 2022
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Familial aplasia of the vermis Benign:2
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Retinal dystrophy Benign:1
Jan 01, 2023
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs71269007; hg19: chr9-139327599; API