3-4753227-G-C

Position:

• chr3-4753227-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378452.1(ITPR1):​c.5545-13303G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.5545-13303G>C		intron_variant		ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.5500-13303G>C		intron_variant			NP_001161744.1
ITPR1	NM_001099952.4	c.5401-13303G>C		intron_variant			NP_001093422.2
ITPR1	NM_002222.7	c.5356-13303G>C		intron_variant			NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.5545-13303G>C		intron_variant			NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.5521-13303G>C		intron_variant		5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.5518-13303G>C		intron_variant				ENSP00000498014.1
ITPR1	ENST00000650294.1	c.5503-13303G>C		intron_variant				ENSP00000498056.1
ITPR1	ENST00000443694.5	c.5500-13303G>C		intron_variant		1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.5473-13303G>C		intron_variant				ENSP00000497026.1
ITPR1	ENST00000357086.10	c.5401-13303G>C		intron_variant		1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.5356-13303G>C		intron_variant		1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.3307-13303G>C		intron_variant				ENSP00000497872.1
ITPR1	ENST00000648431.1	c.2845-13303G>C		intron_variant				ENSP00000498149.1
ITPR1	ENST00000648212.1	c.2452-13303G>C		intron_variant				ENSP00000498022.1

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.057
DANN	Benign	0.46

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: rs746039; hg19: chr3-4794911;