rs181465598

Variant names:

• chr3-4667556-C-G
• NM_001378452.1:c.1886+7C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-4667556-C-G
• chr3-4667556-C-T

Variant summary

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

The NM_001378452.1(ITPR1):​c.1886+7C>G variant causes a splice region, 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. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITPR1 NM_001378452.1 splice_region, intron
• Scores: Splicing: ADA: 0.00006074
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.620

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 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 rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.1886+7C>G		splice_region_variant, intron_variant	Intron 18 of 61	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.1841+7C>G		splice_region_variant, intron_variant	Intron 17 of 60		NP_001161744.1
ITPR1	NM_001099952.4	c.1886+7C>G		splice_region_variant, intron_variant	Intron 18 of 58		NP_001093422.2
ITPR1	NM_002222.7	c.1841+7C>G		splice_region_variant, intron_variant	Intron 17 of 57		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.1886+7C>G		splice_region_variant, intron_variant	Intron 18 of 61		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.1886+7C>G		splice_region_variant, intron_variant	Intron 18 of 61	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.1886+7C>G		splice_region_variant, intron_variant	Intron 18 of 61			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.1841+7C>G		splice_region_variant, intron_variant	Intron 17 of 60			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.1841+7C>G		splice_region_variant, intron_variant	Intron 17 of 60	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.1841+7C>G		splice_region_variant, intron_variant	Intron 15 of 58			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.1886+7C>G		splice_region_variant, intron_variant	Intron 18 of 58	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.1841+7C>G		splice_region_variant, intron_variant	Intron 17 of 57	1		ENSP00000397885.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Sep 17, 2021

Athena Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.50
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000061
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: -30

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-4709240;