3-4516331-A-G

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.-16-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 524,368 control chromosomes in the GnomAD database, including 6,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1540 hom., cov: 33)
  • Exomes 𝑓: 0.16 (5331 hom.)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69

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=-0.78).
• BP6: Variant 3-4516331-A-G is Benign according to our data. Variant chr3-4516331-A-G is described in ClinVar as [Benign]. Clinvar id is 1293508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR1	NM_001378452.1	c.-16-145A>G		intron_variant		ENST00000649015.2
ITPR1	NM_001099952.4	c.-16-145A>G		intron_variant
ITPR1	NM_001168272.2	c.-16-145A>G		intron_variant
ITPR1	NM_002222.7	c.-16-145A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR1	ENST00000649015.2	c.-16-145A>G		intron_variant			NM_001378452.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19268 AN: 152118 Hom.: 1540 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.155 AC: 57853 AN: 372132 Hom.: 5331 AF XY: 0.152 AC XY: 29697 AN XY: 194834

Gnomad4 AFR exome AF: 0.0321

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.0869

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.127 AC: 19266 AN: 152236 Hom.: 1540 Cov.: 33 AF XY: 0.124 AC XY: 9195 AN XY: 74426

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.129

Alfa AF: 0.161 Hom.: 555

Bravo AF: 0.121

Asia WGS AF: 0.0420 AC: 146 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	14
Dann	Benign	0.56

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: rs56378811; hg19: chr3-4558015;