NM_001378452.1:c.4281+108C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001378452.1(ITPR1):c.4281+108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,170,966 control chromosomes in the GnomAD database, including 7,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.089 ( 783 hom., cov: 33)

Exomes 𝑓: 0.11 ( 7155 hom. )

Consequence

ITPR1
NM_001378452.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0440

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

aniridia-cerebellar ataxia-intellectual disability syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
spinocerebellar ataxia type 29
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
spinocerebellar ataxia type 15/16
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ITPR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-4693849-C-T is Benign according to our data. Variant chr3-4693849-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258510.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ITPR1	NM_001378452.1 link	c.4281+108C>T	intron_variant	Intron 33 of 61	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2 link	c.4236+108C>T	intron_variant	Intron 32 of 60		NP_001161744.1
ITPR1	NM_001099952.4 link	c.4254+108C>T	intron_variant	Intron 33 of 58		NP_001093422.2
ITPR1	NM_002222.7 link	c.4209+108C>T	intron_variant	Intron 32 of 57		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ITPR1	ENST00000649015.2 link	c.4281+108C>T	intron_variant	Intron 33 of 61		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12 link	c.4254+108C>T	intron_variant	Intron 33 of 61	5		ENSP00000346595.8
ITPR1	ENST00000648266.1 link	c.4254+108C>T	intron_variant	Intron 33 of 61			ENSP00000498014.1
ITPR1	ENST00000650294.1 link	c.4236+108C>T	intron_variant	Intron 32 of 60			ENSP00000498056.1
ITPR1	ENST00000443694.5 link	c.4236+108C>T	intron_variant	Intron 32 of 60	1		ENSP00000401671.2
ITPR1	ENST00000648309.1 link	c.4209+108C>T	intron_variant	Intron 30 of 58			ENSP00000497026.1
ITPR1	ENST00000357086.10 link	c.4254+108C>T	intron_variant	Intron 33 of 58	1		ENSP00000349597.4
ITPR1	ENST00000456211.8 link	c.4209+108C>T	intron_variant	Intron 32 of 57	1		ENSP00000397885.2
ITPR1	ENST00000648038.1 link	c.2091+108C>T	intron_variant	Intron 14 of 41			ENSP00000497872.1
ITPR1	ENST00000648431.1 link	c.1581+108C>T	intron_variant	Intron 11 of 38			ENSP00000498149.1
ITPR1	ENST00000648212.1 link	c.1188+108C>T	intron_variant	Intron 9 of 38			ENSP00000498022.1

Frequencies

GnomAD3 genomes

AF:

0.0893

AC:

13585

AN:

152130

Hom.:

781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0928

Gnomad EAS

AF:

0.0140

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0997

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0979

GnomAD4 exome

AF:

0.115

AC:

117035

AN:

1018718

Hom.:

7155

AF XY:

0.115

AC XY:

58021

AN XY:

502792

show subpopulations

African (AFR)

AF:

0.0164

AC:

384

AN:

23348

American (AMR)

AF:

0.134

AC:

3243

AN:

24234

Ashkenazi Jewish (ASJ)

AF:

0.0957

AC:

1704

AN:

17810

East Asian (EAS)

AF:

0.0103

AC:

346

AN:

33516

South Asian (SAS)

AF:

0.118

AC:

6851

AN:

57836

European-Finnish (FIN)

AF:

0.105

AC:

3987

AN:

38082

Middle Eastern (MID)

AF:

0.115

AC:

383

AN:

3330

European-Non Finnish (NFE)

AF:

0.123

AC:

95380

AN:

775978

Other (OTH)

AF:

0.107

AC:

4757

AN:

44584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4962

9924

14886

19848

24810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3246

6492

9738

12984

16230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0894

AC:

13604

AN:

152248

Hom.:

783

Cov.:

AF XY:

0.0879

AC XY:

6547

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0213

AC:

886

AN:

41566

American (AMR)

AF:

0.127

AC:

1940

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0928

AC:

322

AN:

3470

East Asian (EAS)

AF:

0.0141

AC:

AN:

5192

South Asian (SAS)

AF:

0.115

AC:

557

AN:

4826

European-Finnish (FIN)

AF:

0.0997

AC:

1056

AN:

10596

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8363

AN:

67988

Other (OTH)

AF:

0.100

AC:

211

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

637

1274

1912

2549

3186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.109

Hom.:

1855

Bravo

AF:

0.0883

Asia WGS

AF:

0.0730

AC:

253

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 10, 2018

GeneDx

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

-0.90

CADD

Benign

0.58

(source)

DANN

Benign

0.66

PhyloP100

-0.044

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over