chr3-4493383-C-G

Variant names:

• chr3-4493383-C-G
• rs572878578
• NM_001378452.1:c.-315C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378452.1(ITPR1):​c.-315C>G variant causes a 5 prime UTR 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: 32)
• Consequence: ITPR1 NM_001378452.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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-DT (HGNC:44470): (ITPR1 divergent transcript)

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=-0.27).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.-315C>G		5_prime_UTR_variant	Exon 1 of 62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015	c.-315C>G		5_prime_UTR_variant	Exon 1 of 62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582	c.-315C>G		5_prime_UTR_variant	Exon 1 of 62	5		ENSP00000346595.8
ITPR1	ENST00000357086	c.-315C>G		5_prime_UTR_variant	Exon 1 of 59	1		ENSP00000349597.4
ITPR1	ENST00000648266.1	c.-315C>G		upstream_gene_variant				ENSP00000498014.1
ITPR1	ENST00000650294.1	c.-315C>G		upstream_gene_variant				ENSP00000498056.1
ITPR1	ENST00000443694.5	c.-315C>G		upstream_gene_variant		1		ENSP00000401671.2
ITPR1	ENST00000456211.8	c.-315C>G		upstream_gene_variant		1		ENSP00000397885.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs572878578; hg19: chr3-4535067;