Variant 3-4691227-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_001378452.1(ITPR1):c.3912C>T(p.His1304His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,064 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: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ITPR1
NM_001378452.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.24

Variant links:

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 links:

ITPR1 (HGNC:):

ITPR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 3-4691227-C-T is Benign according to our data. Variant chr3-4691227-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1596309.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.24 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1 linkuse as main transcript	c.3912C>T	p.His1304His	synonymous_variant	32/62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2 linkuse as main transcript	c.3867C>T	p.His1289His	synonymous_variant	31/61		NP_001161744.1	Q14643-2
ITPR1	NM_001099952.4 linkuse as main transcript	c.3885C>T	p.His1295His	synonymous_variant	32/59		NP_001093422.2	Q14643-3B4DER3Q59H91
ITPR1	NM_002222.7 linkuse as main transcript	c.3840C>T	p.His1280His	synonymous_variant	31/58		NP_002213.5	Q14643-4B4DER3B4DGH1Q59H91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITPR1	ENST00000649015.2 linkuse as main transcript	c.3912C>T	p.His1304His	synonymous_variant	32/62		NM_001378452.1	ENSP00000497605.1	Q14643-1
ITPR1	ENST00000354582.12 linkuse as main transcript	c.3885C>T	p.His1295His	synonymous_variant	32/62	5		ENSP00000346595.8	A0A3F2YNW8
ITPR1	ENST00000648266.1 linkuse as main transcript	c.3885C>T	p.His1295His	synonymous_variant	32/62			ENSP00000498014.1	A0A3B3IU04
ITPR1	ENST00000650294.1 linkuse as main transcript	c.3867C>T	p.His1289His	synonymous_variant	31/61			ENSP00000498056.1	A0A3B3ITU8
ITPR1	ENST00000443694.5 linkuse as main transcript	c.3867C>T	p.His1289His	synonymous_variant	31/61	1		ENSP00000401671.2	Q14643-2
ITPR1	ENST00000648309.1 linkuse as main transcript	c.3840C>T	p.His1280His	synonymous_variant	29/59			ENSP00000497026.1	Q14643-5
ITPR1	ENST00000357086.10 linkuse as main transcript	c.3885C>T	p.His1295His	synonymous_variant	32/59	1		ENSP00000349597.4	Q14643-3
ITPR1	ENST00000456211.8 linkuse as main transcript	c.3840C>T	p.His1280His	synonymous_variant	31/58	1		ENSP00000397885.2	Q14643-4
ITPR1	ENST00000648038.1 linkuse as main transcript	c.1722C>T	p.His574His	synonymous_variant	13/42			ENSP00000497872.1	A0A3B3ITQ1
ITPR1	ENST00000648431.1 linkuse as main transcript	c.1212C>T	p.His404His	synonymous_variant	10/39			ENSP00000498149.1	A0A3B3IU05
ITPR1	ENST00000648212.1 linkuse as main transcript	c.819C>T	p.His273His	synonymous_variant	8/39			ENSP00000498022.1	A0A3B3IU13

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

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:

0.0000241

AC:

AN:

248498

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.0000355

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000722

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:

0.0000225

Hom.:

Bravo

AF:

0.0000340

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000595

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.1

DANN

Benign

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over