rs10510297

Positions:

• chr3-4762316-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378452.1(ITPR1):​c.5545-4214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,070 control chromosomes in the GnomAD database, including 7,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7056 hom., cov: 32)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR1	NM_001378452.1	c.5545-4214C>T		intron_variant		ENST00000649015.2
ITPR1	NM_001099952.4	c.5401-4214C>T		intron_variant
ITPR1	NM_001168272.2	c.5500-4214C>T		intron_variant
ITPR1	NM_002222.7	c.5356-4214C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR1	ENST00000649015.2	c.5545-4214C>T		intron_variant			NM_001378452.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43846 AN: 151952 Hom.: 7057 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.288 AC: 43849 AN: 152070 Hom.: 7056 Cov.: 32 AF XY: 0.290 AC XY: 21527 AN XY: 74334

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0524

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.261

Alfa AF: 0.338 Hom.: 12131

Bravo AF: 0.268

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.53

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: rs10510297; hg19: chr3-4804000;