chr3-4782678-C-T

Position:

• chr3-4782678-C-T

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.6447C>T​(p.Asn2149Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000786 in 1,603,232 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (1 hom.)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.01

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 3-4782678-C-T is Benign according to our data. Variant chr3-4782678-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 447596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.6447C>T	p.Asn2149Asn	synonymous_variant	50/62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.6402C>T	p.Asn2134Asn	synonymous_variant	49/61		NP_001161744.1
ITPR1	NM_001099952.4	c.6303C>T	p.Asn2101Asn	synonymous_variant	47/59		NP_001093422.2
ITPR1	NM_002222.7	c.6258C>T	p.Asn2086Asn	synonymous_variant	46/58		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.6447C>T	p.Asn2149Asn	synonymous_variant	50/62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.6423C>T	p.Asn2141Asn	synonymous_variant	50/62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.6420C>T	p.Asn2140Asn	synonymous_variant	50/62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.6405C>T	p.Asn2135Asn	synonymous_variant	49/61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.6402C>T	p.Asn2134Asn	synonymous_variant	49/61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.6375C>T	p.Asn2125Asn	synonymous_variant	47/59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.6303C>T	p.Asn2101Asn	synonymous_variant	47/59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.6258C>T	p.Asn2086Asn	synonymous_variant	46/58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.4209C>T	p.Asn1403Asn	synonymous_variant	30/42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.3747C>T	p.Asn1249Asn	synonymous_variant	28/39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.3354C>T	p.Asn1118Asn	synonymous_variant	26/39			ENSP00000498022.1

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 48 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.0000910 AC: 22 AN: 241770 Hom.: 0 AF XY: 0.0000914 AC XY: 12 AN XY: 131342

Gnomad AFR exome AF: 0.000933

Gnomad AMR exome AF: 0.000153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000588

Gnomad SAS exome AF: 0.0000339

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000538 AC: 78 AN: 1450976 Hom.: 1 Cov.: 30 AF XY: 0.0000485 AC XY: 35 AN XY: 721506

Gnomad4 AFR exome AF: 0.00121

Gnomad4 AMR exome AF: 0.000160

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.0000237

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000181

Gnomad4 OTH exome AF: 0.0000667

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74436

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000231 Hom.: 0

Bravo AF: 0.000382

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 16, 2017

- -

ITPR1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.1
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs202123078; hg19: chr3-4824362;