rs3805006

Positions:

• chr3-4759085-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.5545-7445T>C		intron_variant		ENST00000649015.2	NP_001365381.1
ITPR1	NM_001099952.4	c.5401-7445T>C		intron_variant			NP_001093422.2
ITPR1	NM_001168272.2	c.5500-7445T>C		intron_variant			NP_001161744.1
ITPR1	NM_002222.7	c.5356-7445T>C		intron_variant			NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.5545-7445T>C		intron_variant			NM_001378452.1	ENSP00000497605

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

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.553

Alfa AF: 0.576 Hom.: 3731

Bravo AF: 0.476

Asia WGS AF: 0.342 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.67

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: rs3805006; hg19: chr3-4800769;