chr3-4814550-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001378452.1(ITPR1):c.7689G>A(p.Lys2563Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,590,260 control chromosomes in the GnomAD database, including 291,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 26468 hom., cov: 24)

Exomes 𝑓: 0.61 ( 265457 hom. )

Consequence

ITPR1
NM_001378452.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.44

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:

ENSG00000235978 (HGNC:):

ENSG00000235978 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-4814550-G-A is Benign according to our data. Variant chr3-4814550-G-A is described in ClinVar as [Benign]. Clinvar id is 129304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-4814550-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1 link	c.7689G>A	p.Lys2563Lys	synonymous_variant	Exon 58 of 62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITPR1	ENST00000649015.2 link	c.7689G>A	p.Lys2563Lys	synonymous_variant	Exon 58 of 62		NM_001378452.1	ENSP00000497605.1	Q14643-1
ITPR1	ENST00000354582.12 link	c.7665G>A	p.Lys2555Lys	synonymous_variant	Exon 58 of 62	5		ENSP00000346595.8	A0A3F2YNW8
ITPR1	ENST00000648266.1 link	c.7662G>A	p.Lys2554Lys	synonymous_variant	Exon 58 of 62			ENSP00000498014.1	A0A3B3IU04
ITPR1	ENST00000650294.1 link	c.7647G>A	p.Lys2549Lys	synonymous_variant	Exon 57 of 61			ENSP00000498056.1	A0A3B3ITU8
ITPR1	ENST00000443694.5 link	c.7644G>A	p.Lys2548Lys	synonymous_variant	Exon 57 of 61	1		ENSP00000401671.2	Q14643-2
ITPR1	ENST00000648309.1 link	c.7617G>A	p.Lys2539Lys	synonymous_variant	Exon 55 of 59			ENSP00000497026.1	Q14643-5
ITPR1	ENST00000357086.10 link	c.7545G>A	p.Lys2515Lys	synonymous_variant	Exon 55 of 59	1		ENSP00000349597.4	Q14643-3
ITPR1	ENST00000456211.8 link	c.7500G>A	p.Lys2500Lys	synonymous_variant	Exon 54 of 58	1		ENSP00000397885.2	Q14643-4
ITPR1	ENST00000648038.1 link	c.5451G>A	p.Lys1817Lys	synonymous_variant	Exon 38 of 42			ENSP00000497872.1	A0A3B3ITQ1
ITPR1	ENST00000648431.1 link	c.4866G>A	p.Lys1622Lys	synonymous_variant	Exon 35 of 39			ENSP00000498149.1	A0A3B3IU05
ITPR1	ENST00000648212.1 link	c.4629G>A	p.Lys1543Lys	synonymous_variant	Exon 35 of 39			ENSP00000498022.1	A0A3B3IU13

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

88686

AN:

148982

Hom.:

26453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.592

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.599

GnomAD3 exomes

AF:

0.604

AC:

149857

AN:

248248

Hom.:

45734

AF XY:

0.605

AC XY:

81516

AN XY:

134688

show subpopulations

Gnomad AFR exome

AF:

0.556

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.586

Gnomad EAS exome

AF:

0.738

Gnomad SAS exome

AF:

0.586

Gnomad FIN exome

AF:

0.642

Gnomad NFE exome

AF:

0.612

Gnomad OTH exome

AF:

0.601

GnomAD4 exome

AF:

0.608

AC:

876888

AN:

1441170

Hom.:

265457

Cov.:

AF XY:

0.609

AC XY:

436309

AN XY:

716730

show subpopulations

Gnomad4 AFR exome

AF:

0.568

Gnomad4 AMR exome

AF:

0.534

Gnomad4 ASJ exome

AF:

0.605

Gnomad4 EAS exome

AF:

0.722

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.653

Gnomad4 NFE exome

AF:

0.608

Gnomad4 OTH exome

AF:

0.607

GnomAD4 genome

AF:

0.595

AC:

88729

AN:

149090

Hom.:

26468

Cov.:

AF XY:

0.594

AC XY:

43117

AN XY:

72560

show subpopulations

Gnomad4 AFR

AF:

0.563

Gnomad4 AMR

AF:

0.549

Gnomad4 ASJ

AF:

0.592

Gnomad4 EAS

AF:

0.722

Gnomad4 SAS

AF:

0.594

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.607

Gnomad4 OTH

AF:

0.592

Alfa

AF:

0.602

Hom.:

43500

Bravo

AF:

0.591

Asia WGS

AF:

0.591

AC:

2056

AN:

3478

EpiCase

AF:

0.601

EpiControl

AF:

0.614

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Jul 15, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gillespie syndrome

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spinocerebellar ataxia type 29

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant cerebellar ataxia

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.7

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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