rs3805006

Variant names:

• chr3-4759085-T-C
• rs3805006
• NM_001378452.1:c.5545-7445T>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.5545-7445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,100 control chromosomes in the GnomAD database, including 22,698 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 0.50 (22698 hom., cov: 32)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 2 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):

• aniridia-cerebellar ataxia-intellectual disability syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• spinocerebellar ataxia type 29

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• spinocerebellar ataxia type 15/16

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 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.5545-7445T>C		intron	N/A	NP_001365381.1	Q14643-1
	ITPR1	NM_001168272.2		c.5500-7445T>C		intron	N/A	NP_001161744.1	Q14643-2
	ITPR1	NM_001099952.4		c.5401-7445T>C		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.5545-7445T>C		intron	N/A	ENSP00000497605.1	Q14643-1
	ITPR1	ENST00000354582.12	TSL:5	c.5521-7445T>C		intron	N/A	ENSP00000346595.8	A0A3F2YNW8
	ITPR1	ENST00000648266.1		c.5518-7445T>C		intron	N/A	ENSP00000498014.1	A0A3B3IU04

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75477 AN: 151982 Hom.: 22695 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.496 AC: 75486 AN: 152100 Hom.: 22698 Cov.: 32 AF XY: 0.493 AC XY: 36626 AN XY: 74336

African (AFR) AF: 0.160 AC: 6636 AN: 41522

American (AMR) AF: 0.528 AC: 8067 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2376 AN: 3464

East Asian (EAS) AF: 0.244 AC: 1260 AN: 5158

South Asian (SAS) AF: 0.452 AC: 2179 AN: 4826

European-Finnish (FIN) AF: 0.634 AC: 6695 AN: 10566

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46215 AN: 67968

Other (OTH) AF: 0.553 AC: 1164 AN: 2106

Alfa AF: 0.561 Hom.: 3782

Bravo AF: 0.476

Asia WGS AF: 0.342 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3805006; hg19: chr3-4800769;