3-4818173-C-A

Position:

• chr3-4818173-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001378452.1(ITPR1):​c.7959C>A​(p.Ile2653Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

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]

ENSG00000235978 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP7: Synonymous conserved (PhyloP=-0.533 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.7959C>A	p.Ile2653Ile	synonymous_variant	60/62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.7959C>A	p.Ile2653Ile	synonymous_variant	60/62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.7935C>A	p.Ile2645Ile	synonymous_variant	60/62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.7932C>A	p.Ile2644Ile	synonymous_variant	60/62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.7917C>A	p.Ile2639Ile	synonymous_variant	59/61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.7914C>A	p.Ile2638Ile	synonymous_variant	59/61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.7887C>A	p.Ile2629Ile	synonymous_variant	57/59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.7815C>A	p.Ile2605Ile	synonymous_variant	57/59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.7770C>A	p.Ile2590Ile	synonymous_variant	56/58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.5721C>A	p.Ile1907Ile	synonymous_variant	40/42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.5136C>A	p.Ile1712Ile	synonymous_variant	37/39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.4899C>A	p.Ile1633Ile	synonymous_variant	37/39			ENSP00000498022.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	5.0
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs371988852; hg19: chr3-4859857;