rs34936112
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_019892.6(INPP5E):c.1280-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,436,530 control chromosomes in the GnomAD database, including 59,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5216 hom., cov: 33)
Exomes 𝑓: 0.29 ( 54578 hom. )
Consequence
INPP5E
NM_019892.6 intron
NM_019892.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.118
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 9-136432610-G-A is Benign according to our data. Variant chr9-136432610-G-A is described in ClinVar as [Benign]. Clinvar id is 261191.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 | UniProt |
---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.1280-24C>T | intron_variant | ENST00000371712.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.1280-24C>T | intron_variant | 1 | NM_019892.6 | P1 | |||
INPP5E | ENST00000676019.1 | c.1178-24C>T | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.254 AC: 38623AN: 151972Hom.: 5215 Cov.: 33
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GnomAD3 exomes AF: 0.257 AC: 39111AN: 152366Hom.: 5628 AF XY: 0.251 AC XY: 20191AN XY: 80538
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GnomAD4 exome AF: 0.285 AC: 366135AN: 1284440Hom.: 54578 Cov.: 19 AF XY: 0.282 AC XY: 180019AN XY: 638958
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GnomAD4 genome ? AF: 0.254 AC: 38642AN: 152090Hom.: 5216 Cov.: 33 AF XY: 0.250 AC XY: 18609AN XY: 74348
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at