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GeneBe

3-4516359-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001378452.1(ITPR1):c.-16-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00844 in 556,064 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 6 hom., cov: 33)
Exomes 𝑓: 0.0089 ( 19 hom. )

Consequence

ITPR1
NM_001378452.1 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.548
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 3-4516359-A-G is Benign according to our data. Variant chr3-4516359-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219513.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00716 (1090/152326) while in subpopulation NFE AF= 0.0103 (701/68036). AF 95% confidence interval is 0.00967. There are 6 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 6 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITPR1NM_001378452.1 linkuse as main transcriptc.-16-117A>G intron_variant ENST00000649015.2
ITPR1NM_001099952.4 linkuse as main transcriptc.-16-117A>G intron_variant
ITPR1NM_001168272.2 linkuse as main transcriptc.-16-117A>G intron_variant
ITPR1NM_002222.7 linkuse as main transcriptc.-16-117A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITPR1ENST00000649015.2 linkuse as main transcriptc.-16-117A>G intron_variant NM_001378452.1 Q14643-1

Frequencies

GnomAD3 genomes
AF:
0.00717
AC:
1092
AN:
152208
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00227
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00825
Gnomad ASJ
AF:
0.00547
Gnomad EAS
AF:
0.00692
Gnomad SAS
AF:
0.00952
Gnomad FIN
AF:
0.00358
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0103
Gnomad OTH
AF:
0.0110
GnomAD4 exome
AF:
0.00892
AC:
3603
AN:
403738
Hom.:
19
AF XY:
0.00907
AC XY:
1925
AN XY:
212332
show subpopulations
Gnomad4 AFR exome
AF:
0.00273
Gnomad4 AMR exome
AF:
0.00634
Gnomad4 ASJ exome
AF:
0.00874
Gnomad4 EAS exome
AF:
0.00258
Gnomad4 SAS exome
AF:
0.0100
Gnomad4 FIN exome
AF:
0.00434
Gnomad4 NFE exome
AF:
0.0104
Gnomad4 OTH exome
AF:
0.00937
GnomAD4 genome
AF:
0.00716
AC:
1090
AN:
152326
Hom.:
6
Cov.:
33
AF XY:
0.00712
AC XY:
530
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00226
Gnomad4 AMR
AF:
0.00824
Gnomad4 ASJ
AF:
0.00547
Gnomad4 EAS
AF:
0.00674
Gnomad4 SAS
AF:
0.00932
Gnomad4 FIN
AF:
0.00358
Gnomad4 NFE
AF:
0.0103
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00990
Hom.:
0
Bravo
AF:
0.00730
Asia WGS
AF:
0.0120
AC:
44
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
18
Dann
Benign
0.79

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.

Other links and lift over

dbSNP: rs73003291; hg19: chr3-4558043; API