3-4766658-A-G

Position:

• chr3-4766658-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378452.1(ITPR1):​c.5673A>G​(p.Gly1891Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.359

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.359 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.5673A>G	p.Gly1891Gly	synonymous_variant	45/62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.5628A>G	p.Gly1876Gly	synonymous_variant	44/61		NP_001161744.1
ITPR1	NM_001099952.4	c.5529A>G	p.Gly1843Gly	synonymous_variant	42/59		NP_001093422.2
ITPR1	NM_002222.7	c.5484A>G	p.Gly1828Gly	synonymous_variant	41/58		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.5673A>G	p.Gly1891Gly	synonymous_variant	45/62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.5649A>G	p.Gly1883Gly	synonymous_variant	45/62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.5646A>G	p.Gly1882Gly	synonymous_variant	45/62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.5631A>G	p.Gly1877Gly	synonymous_variant	44/61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.5628A>G	p.Gly1876Gly	synonymous_variant	44/61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.5601A>G	p.Gly1867Gly	synonymous_variant	42/59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.5529A>G	p.Gly1843Gly	synonymous_variant	42/59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.5484A>G	p.Gly1828Gly	synonymous_variant	41/58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.3435A>G	p.Gly1145Gly	synonymous_variant	25/42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.2973A>G	p.Gly991Gly	synonymous_variant	23/39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.2580A>G	p.Gly860Gly	synonymous_variant	21/39			ENSP00000498022.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 30, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.1
DANN	Benign	0.70

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: rs1553735513; hg19: chr3-4808342;