rs777975463

Variant names:

• chr3-4815205-G-A
• rs777975463
• NM_001378452.1:c.7854G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-4815205-G-A
• chr3-4815205-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001378452.1(ITPR1):​c.7854G>A​(p.Thr2618Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.57

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 3-4815205-G-A is Benign according to our data. Variant chr3-4815205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.7854G>A	p.Thr2618Thr	synonymous_variant	Exon 59 of 62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.7854G>A	p.Thr2618Thr	synonymous_variant	Exon 59 of 62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.7830G>A	p.Thr2610Thr	synonymous_variant	Exon 59 of 62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.7827G>A	p.Thr2609Thr	synonymous_variant	Exon 59 of 62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.7812G>A	p.Thr2604Thr	synonymous_variant	Exon 58 of 61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.7809G>A	p.Thr2603Thr	synonymous_variant	Exon 58 of 61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.7782G>A	p.Thr2594Thr	synonymous_variant	Exon 56 of 59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.7710G>A	p.Thr2570Thr	synonymous_variant	Exon 56 of 59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.7665G>A	p.Thr2555Thr	synonymous_variant	Exon 55 of 58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.5616G>A	p.Thr1872Thr	synonymous_variant	Exon 39 of 42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.5031G>A	p.Thr1677Thr	synonymous_variant	Exon 36 of 39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.4794G>A	p.Thr1598Thr	synonymous_variant	Exon 36 of 39			ENSP00000498022.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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

GnomAD3 exomes AF: 0.0000201 AC: 5 AN: 249114 Hom.: 0 AF XY: 0.0000370 AC XY: 5 AN XY: 135138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 727072

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

Gnomad4 AFR AF: 0.0000724

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

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 30, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Feb 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.17
DANN	Benign	0.89
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: rs777975463; hg19: chr3-4856889;