rs6442905

Variant summary

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

The NM_001378452.1(ITPR1):c.6111T>C(p.Asn2037=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,613,740 control chromosomes in the GnomAD database, including 761,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71220 hom., cov: 32)

Exomes 𝑓: 0.97 ( 689891 hom. )

Consequence

ITPR1
NM_001378452.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.09

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=-0.67).

BP6

Variant 3-4775373-T-C is Benign according to our data. Variant chr3-4775373-T-C is described in ClinVar as [Benign]. Clinvar id is 1170008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-4775373-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ITPR1	NM_001378452.1 linkuse as main transcript	c.6111T>C	p.Asn2037=	synonymous_variant	47/62	ENST00000649015.2
ITPR1	NM_001168272.2 linkuse as main transcript	c.6066T>C	p.Asn2022=	synonymous_variant	46/61
ITPR1	NM_001099952.4 linkuse as main transcript	c.5967T>C	p.Asn1989=	synonymous_variant	44/59
ITPR1	NM_002222.7 linkuse as main transcript	c.5922T>C	p.Asn1974=	synonymous_variant	43/58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR1	ENST00000649015.2 linkuse as main transcript	c.6111T>C	p.Asn2037=	synonymous_variant	47/62		NM_001378452.1		Q14643-1

Frequencies

GnomAD3 genomes

AF:

0.967

AC:

147172

AN:

152216

Hom.:

71164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.954

Gnomad AMI

AF:

0.976

Gnomad AMR

AF:

0.966

Gnomad ASJ

AF:

0.950

Gnomad EAS

AF:

0.985

Gnomad SAS

AF:

0.956

Gnomad FIN

AF:

0.992

Gnomad MID

AF:

0.959

Gnomad NFE

AF:

0.972

Gnomad OTH

AF:

0.959

GnomAD3 exomes

AF:

0.971

AC:

242087

AN:

249286

Hom.:

117599

AF XY:

0.970

AC XY:

131193

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.954

Gnomad AMR exome

AF:

0.977

Gnomad ASJ exome

AF:

0.954

Gnomad EAS exome

AF:

0.987

Gnomad SAS exome

AF:

0.959

Gnomad FIN exome

AF:

0.992

Gnomad NFE exome

AF:

0.970

Gnomad OTH exome

AF:

0.967

GnomAD4 exome

AF:

0.972

AC:

1419914

AN:

1461406

Hom.:

689891

Cov.:

AF XY:

0.971

AC XY:

706047

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.954

Gnomad4 AMR exome

AF:

0.975

Gnomad4 ASJ exome

AF:

0.954

Gnomad4 EAS exome

AF:

0.989

Gnomad4 SAS exome

AF:

0.960

Gnomad4 FIN exome

AF:

0.991

Gnomad4 NFE exome

AF:

0.972

Gnomad4 OTH exome

AF:

0.968

GnomAD4 genome

AF:

0.967

AC:

147287

AN:

152334

Hom.:

71220

Cov.:

AF XY:

0.967

AC XY:

72066

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.954

Gnomad4 AMR

AF:

0.966

Gnomad4 ASJ

AF:

0.950

Gnomad4 EAS

AF:

0.985

Gnomad4 SAS

AF:

0.956

Gnomad4 FIN

AF:

0.992

Gnomad4 NFE

AF:

0.972

Gnomad4 OTH

AF:

0.960

Alfa

AF:

0.968

Hom.:

46718

Bravo

AF:

0.964

Asia WGS

AF:

0.966

AC:

3360

AN:

3478

EpiCase

AF:

0.965

EpiControl

AF:

0.967

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	-	- -

Gillespie syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Spinocerebellar ataxia type 29

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

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

-0.67

Cadd

Benign

0.15

Dann

Benign

0.26

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