rs371988852

Variant names:

• chr3-4818173-C-A
• rs371988852
• NM_001378452.1:c.7959C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-4818173-C-A
• chr3-4818173-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001378452.1(ITPR1):​c.7959C>A​(p.Ile2653Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I2653I) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 0 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: Ambry Genetics, G2P, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• spinocerebellar ataxia type 29

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

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

ENSG00000235978 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP7: Synonymous conserved (PhyloP=-0.533 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.7959C>A	p.Ile2653Ile	synonymous_variant	Exon 60 of 62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.7959C>A	p.Ile2653Ile	synonymous_variant	Exon 60 of 62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.7935C>A	p.Ile2645Ile	synonymous_variant	Exon 60 of 62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.7932C>A	p.Ile2644Ile	synonymous_variant	Exon 60 of 62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.7917C>A	p.Ile2639Ile	synonymous_variant	Exon 59 of 61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.7914C>A	p.Ile2638Ile	synonymous_variant	Exon 59 of 61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.7887C>A	p.Ile2629Ile	synonymous_variant	Exon 57 of 59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.7815C>A	p.Ile2605Ile	synonymous_variant	Exon 57 of 59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.7770C>A	p.Ile2590Ile	synonymous_variant	Exon 56 of 58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.5721C>A	p.Ile1907Ile	synonymous_variant	Exon 40 of 42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.5136C>A	p.Ile1712Ile	synonymous_variant	Exon 37 of 39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.4899C>A	p.Ile1633Ile	synonymous_variant	Exon 37 of 39			ENSP00000498022.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs371988852; hg19: chr3-4859857;