chr3-4787891-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378452.1(ITPR1):c.6616-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,269,810 control chromosomes in the GnomAD database, including 9,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 643 hom., cov: 31)

Exomes 𝑓: 0.12 ( 8946 hom. )

Consequence

ITPR1
NM_001378452.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.39

Publications

5 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:

ENSG00000235978 (HGNC:):

ENSG00000235978 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-4787891-T-C is Benign according to our data. Variant chr3-4787891-T-C is described in ClinVar as Benign. ClinVar VariationId is 1240984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ITPR1	NM_001378452.1 link	c.6616-56T>C	intron_variant	Intron 51 of 61	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2 link	c.6571-56T>C	intron_variant	Intron 50 of 60		NP_001161744.1
ITPR1	NM_001099952.4 link	c.6472-56T>C	intron_variant	Intron 48 of 58		NP_001093422.2
ITPR1	NM_002222.7 link	c.6427-56T>C	intron_variant	Intron 47 of 57		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ITPR1	ENST00000649015.2 link	c.6616-56T>C	intron_variant	Intron 51 of 61		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12 link	c.6592-56T>C	intron_variant	Intron 51 of 61	5		ENSP00000346595.8
ITPR1	ENST00000648266.1 link	c.6589-56T>C	intron_variant	Intron 51 of 61			ENSP00000498014.1
ITPR1	ENST00000650294.1 link	c.6574-56T>C	intron_variant	Intron 50 of 60			ENSP00000498056.1
ITPR1	ENST00000443694.5 link	c.6571-56T>C	intron_variant	Intron 50 of 60	1		ENSP00000401671.2
ITPR1	ENST00000648309.1 link	c.6544-56T>C	intron_variant	Intron 48 of 58			ENSP00000497026.1
ITPR1	ENST00000357086.10 link	c.6472-56T>C	intron_variant	Intron 48 of 58	1		ENSP00000349597.4
ITPR1	ENST00000456211.8 link	c.6427-56T>C	intron_variant	Intron 47 of 57	1		ENSP00000397885.2
ITPR1	ENST00000648038.1 link	c.4378-56T>C	intron_variant	Intron 31 of 41			ENSP00000497872.1
ITPR1	ENST00000648431.1 link	c.3916-56T>C	intron_variant	Intron 29 of 38			ENSP00000498149.1
ITPR1	ENST00000648212.1 link	c.3523-56T>C	intron_variant	Intron 27 of 38			ENSP00000498022.1

Frequencies

GnomAD3 genomes

AF:

0.0818

AC:

12404

AN:

151686

Hom.:

644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.0684

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0874

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.0846

GnomAD4 exome

AF:

0.117

AC:

131215

AN:

1118006

Hom.:

8946

AF XY:

0.115

AC XY:

64700

AN XY:

564900

show subpopulations

African (AFR)

AF:

0.0199

AC:

507

AN:

25532

American (AMR)

AF:

0.0504

AC:

1568

AN:

31140

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2508

AN:

22958

East Asian (EAS)

AF:

0.000168

AC:

AN:

35694

South Asian (SAS)

AF:

0.0328

AC:

2286

AN:

69720

European-Finnish (FIN)

AF:

0.0916

AC:

4620

AN:

50452

Middle Eastern (MID)

AF:

0.0639

AC:

317

AN:

4964

European-Non Finnish (NFE)

AF:

0.138

AC:

114282

AN:

828950

Other (OTH)

AF:

0.105

AC:

5121

AN:

48596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5610

11220

16831

22441

28051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3644

7288

10932

14576

18220

<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:

0.0817

AC:

12402

AN:

151804

Hom.:

643

Cov.:

AF XY:

0.0779

AC XY:

5781

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.0245

AC:

1016

AN:

41398

American (AMR)

AF:

0.0682

AC:

1040

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

374

AN:

3470

East Asian (EAS)

AF:

0.000966

AC:

AN:

5176

South Asian (SAS)

AF:

0.0294

AC:

141

AN:

4790

European-Finnish (FIN)

AF:

0.0874

AC:

921

AN:

10538

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8566

AN:

67878

Other (OTH)

AF:

0.0833

AC:

175

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

551

1101

1652

2202

2753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.112

Hom.:

1784

Bravo

AF:

0.0779

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 31, 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

-0.86

CADD

Benign

0.56

(source)

DANN

Benign

0.36

PhyloP100

-1.4

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