rs746039

Variant names:

• chr3-4753227-G-A
• rs746039
• NM_001378452.1:c.5545-13303G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-4753227-G-A
• chr3-4753227-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378452.1(ITPR1):​c.5545-13303G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 151,918 control chromosomes in the GnomAD database, including 51,915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (51915 hom., cov: 29)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 29

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• aniridia-cerebellar ataxia-intellectual disability syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Genomics England PanelApp
• spinocerebellar ataxia type 15/16

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378452.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR1	NM_001378452.1	MANE Select	c.5545-13303G>A		intron	N/A	NP_001365381.1	Q14643-1
	ITPR1	NM_001168272.2		c.5500-13303G>A		intron	N/A	NP_001161744.1	Q14643-2
	ITPR1	NM_001099952.4		c.5401-13303G>A		intron	N/A	NP_001093422.2	Q14643-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR1	ENST00000649015.2	MANE Select	c.5545-13303G>A		intron	N/A	ENSP00000497605.1	Q14643-1
	ITPR1	ENST00000354582.12	TSL:5	c.5521-13303G>A		intron	N/A	ENSP00000346595.8	A0A3F2YNW8
	ITPR1	ENST00000648266.1		c.5518-13303G>A		intron	N/A	ENSP00000498014.1	A0A3B3IU04

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125335 AN: 151800 Hom.: 51872 Cov.: 29

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.826 AC: 125433 AN: 151918 Hom.: 51915 Cov.: 29 AF XY: 0.829 AC XY: 61532 AN XY: 74254

African (AFR) AF: 0.872 AC: 36127 AN: 41416

American (AMR) AF: 0.837 AC: 12786 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2869 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5101 AN: 5130

South Asian (SAS) AF: 0.829 AC: 3991 AN: 4812

European-Finnish (FIN) AF: 0.816 AC: 8611 AN: 10556

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53215 AN: 67942

Other (OTH) AF: 0.821 AC: 1735 AN: 2112

Alfa AF: 0.798 Hom.: 104116

Bravo AF: 0.832

Asia WGS AF: 0.892 AC: 3105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.079
DANN	Benign	0.71
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs746039; hg19: chr3-4794911;