rs61757108
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_001378452.1(ITPR1):c.3921C>T(p.His1307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,612,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00039 ( 1 hom. )
Consequence
ITPR1
NM_001378452.1 synonymous
NM_001378452.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.73
Genes affected
ITPR1 (HGNC:6180): (inositol 1,4,5-trisphosphate receptor type 1) This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
Variant 3-4691236-C-T is Benign according to our data. Variant chr3-4691236-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 284759.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=4, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=2.73 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.3921C>T | p.His1307= | synonymous_variant | 32/62 | ENST00000649015.2 | |
ITPR1 | NM_001168272.2 | c.3876C>T | p.His1292= | synonymous_variant | 31/61 | ||
ITPR1 | NM_001099952.4 | c.3894C>T | p.His1298= | synonymous_variant | 32/59 | ||
ITPR1 | NM_002222.7 | c.3849C>T | p.His1283= | synonymous_variant | 31/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.3921C>T | p.His1307= | synonymous_variant | 32/62 | NM_001378452.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000270 AC: 67AN: 248546Hom.: 1 AF XY: 0.000245 AC XY: 33AN XY: 134818
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GnomAD4 exome AF: 0.000390 AC: 569AN: 1460580Hom.: 1 Cov.: 30 AF XY: 0.000366 AC XY: 266AN XY: 726562
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GnomAD4 genome ? AF: 0.000322 AC: 49AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000336 AC XY: 25AN XY: 74492
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | ITPR1: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 25, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 07, 2021 | - - |
ITPR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 15, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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