rs2306877

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378452.1(ITPR1):c.2658A>C(p.Leu886=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,605,562 control chromosomes in the GnomAD database, including 43,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5980 hom., cov: 32)

Exomes 𝑓: 0.21 ( 37154 hom. )

Consequence

ITPR1
NM_001378452.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.52

Variant links:

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]

ITPR1 links:

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=-0.88).

BP6

Variant 3-4675127-A-C is Benign according to our data. Variant chr3-4675127-A-C is described in ClinVar as [Benign]. Clinvar id is 129299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-4675127-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ITPR1	NM_001378452.1 linkuse as main transcript	c.2658A>C	p.Leu886=	synonymous_variant	23/62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2 linkuse as main transcript	c.2613A>C	p.Leu871=	synonymous_variant	22/61		NP_001161744.1
ITPR1	NM_001099952.4 linkuse as main transcript	c.2658A>C	p.Leu886=	synonymous_variant	23/59		NP_001093422.2
ITPR1	NM_002222.7 linkuse as main transcript	c.2613A>C	p.Leu871=	synonymous_variant	22/58		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2 linkuse as main transcript	c.2658A>C	p.Leu886=	synonymous_variant	23/62		NM_001378452.1	ENSP00000497605		Q14643-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40967

AN:

151992

Hom.:

5968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.271

AC:

67189

AN:

247978

Hom.:

10383

AF XY:

0.266

AC XY:

35786

AN XY:

134610

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.417

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.214

AC:

310432

AN:

1453452

Hom.:

37154

Cov.:

AF XY:

0.217

AC XY:

157259

AN XY:

723564

show subpopulations

Gnomad4 AFR exome

AF:

0.374

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.270

AC:

41031

AN:

152110

Hom.:

5980

Cov.:

AF XY:

0.276

AC XY:

20548

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.207

Hom.:

5976

Bravo

AF:

0.272

Asia WGS

AF:

0.359

AC:

1245

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

not specified

Benign:1

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. -

Gillespie syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Spinocerebellar ataxia type 29

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Autosomal dominant cerebellar ataxia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Spinocerebellar ataxia type 15/16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.1

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 13

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