Variant 3-4516420-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378452.1(ITPR1):c.-16-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 946,352 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 710 hom., cov: 33)

Exomes 𝑓: 0.014 ( 318 hom. )

Consequence

ITPR1
NM_001378452.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.85

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 3-4516420-T-C is Benign according to our data. Variant chr3-4516420-T-C is described in ClinVar as [Benign]. Clinvar id is 1269017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ITPR1	NM_001378452.1 linkuse as main transcript	c.-16-56T>C	intron_variant	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001099952.4 linkuse as main transcript	c.-16-56T>C	intron_variant		NP_001093422.2
ITPR1	NM_001168272.2 linkuse as main transcript	c.-16-56T>C	intron_variant		NP_001161744.1
ITPR1	NM_002222.7 linkuse as main transcript	c.-16-56T>C	intron_variant		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2 linkuse as main transcript	c.-16-56T>C		intron_variant			NM_001378452.1	ENSP00000497605		Q14643-1

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8826

AN:

152178

Hom.:

701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0291

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00692

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0430

GnomAD4 exome

AF:

0.0137

AC:

10906

AN:

794056

Hom.:

318

AF XY:

0.0134

AC XY:

5455

AN XY:

408470

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.0160

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.00296

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.00425

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0582

AC:

8859

AN:

152296

Hom.:

710

Cov.:

AF XY:

0.0565

AC XY:

4207

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.0291

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00674

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0174

Hom.:

Bravo

AF:

0.0642

Asia WGS

AF:

0.0230

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.18

DANN

Benign

0.87

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