3-4516420-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.85

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR1	NM_001378452.1	c.-16-56T>C		intron_variant		ENST00000649015.2
ITPR1	NM_001099952.4	c.-16-56T>C		intron_variant
ITPR1	NM_001168272.2	c.-16-56T>C		intron_variant
ITPR1	NM_002222.7	c.-16-56T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR1	ENST00000649015.2	c.-16-56T>C		intron_variant			NM_001378452.1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8826 AN: 152178 Hom.: 701 Cov.: 33

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

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.: 33 AF XY: 0.0565 AC XY: 4207 AN XY: 74474

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.: 26

Bravo AF: 0.0642

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

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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

Other links and lift over

dbSNP: rs9829878; hg19: chr3-4558104;