rs4073665

Positions:

• chr3-4640545-G-A
• chr3-4640545-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378452.1(ITPR1):​c.366+1075G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,202 control chromosomes in the GnomAD database, including 53,396 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 0.84 (53396 hom., cov: 32)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR1	NM_001378452.1	c.366+1075G>A		intron_variant		ENST00000649015.2
ITPR1	NM_001099952.4	c.366+1075G>A		intron_variant
ITPR1	NM_001168272.2	c.366+1075G>A		intron_variant
ITPR1	NM_002222.7	c.366+1075G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR1	ENST00000649015.2	c.366+1075G>A		intron_variant			NM_001378452.1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 127063 AN: 152084 Hom.: 53376 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.835 AC: 127136 AN: 152202 Hom.: 53396 Cov.: 32 AF XY: 0.838 AC XY: 62357 AN XY: 74428

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.835

Alfa AF: 0.859 Hom.: 76436

Bravo AF: 0.826

Asia WGS AF: 0.853 AC: 2966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.44
DANN	Benign	0.25

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: rs4073665; hg19: chr3-4682229;