chr3-4800547-C-T

Position:

chr3-4800547-C-T

Variant summary

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

The NM_001378452.1(ITPR1):c.7054C>T(p.Leu2352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,613,528 control chromosomes in the GnomAD database, including 66,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5109 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61376 hom. )

Consequence

ITPR1
NM_001378452.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.0270

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-4800547-C-T is Benign according to our data. Variant chr3-4800547-C-T is described in ClinVar as [Benign]. Clinvar id is 129302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-4800547-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.027 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ITPR1	NM_001378452.1 linkuse as main transcript	c.7054C>T	p.Leu2352=	synonymous_variant	54/62	ENST00000649015.2
ITPR1	NM_001168272.2 linkuse as main transcript	c.7009C>T	p.Leu2337=	synonymous_variant	53/61
ITPR1	NM_001099952.4 linkuse as main transcript	c.6910C>T	p.Leu2304=	synonymous_variant	51/59
ITPR1	NM_002222.7 linkuse as main transcript	c.6865C>T	p.Leu2289=	synonymous_variant	50/58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR1	ENST00000649015.2 linkuse as main transcript	c.7054C>T	p.Leu2352=	synonymous_variant	54/62		NM_001378452.1		Q14643-1
	ENST00000693140.1 linkuse as main transcript	n.582-6991G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37797

AN:

152088

Hom.:

5099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.273

GnomAD3 exomes

AF:

0.293

AC:

73061

AN:

249164

Hom.:

11290

AF XY:

0.292

AC XY:

39537

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.283

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.286

AC:

418458

AN:

1461322

Hom.:

61376

Cov.:

AF XY:

0.286

AC XY:

208252

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.249

AC:

37856

AN:

152206

Hom.:

5109

Cov.:

AF XY:

0.249

AC XY:

18493

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.325

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.274

Hom.:

9962

Bravo

AF:

0.252

Asia WGS

AF:

0.306

AC:

1068

AN:

3478

EpiCase

AF:

0.294

EpiControl

AF:

0.293

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	Sep 04, 2019	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

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 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. -

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

-0.51

CADD

Benign

0.45

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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