rs34491089
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001378452.1(ITPR1):āc.6696A>Gā(p.Lys2232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,612,788 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.021 ( 59 hom., cov: 31)
Exomes š: 0.026 ( 656 hom. )
Consequence
ITPR1
NM_001378452.1 synonymous
NM_001378452.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.576
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 3-4788027-A-G is Benign according to our data. Variant chr3-4788027-A-G is described in ClinVar as [Benign]. Clinvar id is 129300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-4788027-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.576 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.6696A>G | p.Lys2232= | synonymous_variant | 52/62 | ENST00000649015.2 | NP_001365381.1 | |
ITPR1 | NM_001168272.2 | c.6651A>G | p.Lys2217= | synonymous_variant | 51/61 | NP_001161744.1 | ||
ITPR1 | NM_001099952.4 | c.6552A>G | p.Lys2184= | synonymous_variant | 49/59 | NP_001093422.2 | ||
ITPR1 | NM_002222.7 | c.6507A>G | p.Lys2169= | synonymous_variant | 48/58 | NP_002213.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.6696A>G | p.Lys2232= | synonymous_variant | 52/62 | NM_001378452.1 | ENSP00000497605 |
Frequencies
GnomAD3 genomes AF: 0.0214 AC: 3262AN: 152222Hom.: 59 Cov.: 31
GnomAD3 genomes
AF:
AC:
3262
AN:
152222
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0302 AC: 7474AN: 247118Hom.: 176 AF XY: 0.0302 AC XY: 4045AN XY: 133916
GnomAD3 exomes
AF:
AC:
7474
AN:
247118
Hom.:
AF XY:
AC XY:
4045
AN XY:
133916
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0265 AC: 38686AN: 1460448Hom.: 656 Cov.: 30 AF XY: 0.0269 AC XY: 19528AN XY: 726386
GnomAD4 exome
AF:
AC:
38686
AN:
1460448
Hom.:
Cov.:
30
AF XY:
AC XY:
19528
AN XY:
726386
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0214 AC: 3262AN: 152340Hom.: 59 Cov.: 31 AF XY: 0.0225 AC XY: 1673AN XY: 74492
GnomAD4 genome
AF:
AC:
3262
AN:
152340
Hom.:
Cov.:
31
AF XY:
AC XY:
1673
AN XY:
74492
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
54
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 31, 2019 | - - |
ITPR1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Autosomal dominant cerebellar ataxia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at