rs886039392

Positions:

• chr3-4645678-C-A
• chr3-4645678-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001378452.1(ITPR1):​c.805C>A​(p.Arg269Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,282 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP7: Synonymous conserved (PhyloP=2.13 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.805C>A	p.Arg269Arg	synonymous_variant	10/62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.805C>A	p.Arg269Arg	synonymous_variant	10/61		NP_001161744.1
ITPR1	NM_001099952.4	c.805C>A	p.Arg269Arg	synonymous_variant	10/59		NP_001093422.2
ITPR1	NM_002222.7	c.805C>A	p.Arg269Arg	synonymous_variant	10/58		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.805C>A	p.Arg269Arg	synonymous_variant	10/62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.805C>A	p.Arg269Arg	synonymous_variant	10/62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.805C>A	p.Arg269Arg	synonymous_variant	10/62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.805C>A	p.Arg269Arg	synonymous_variant	10/61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.805C>A	p.Arg269Arg	synonymous_variant	10/61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.805C>A	p.Arg269Arg	synonymous_variant	8/59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.805C>A	p.Arg269Arg	synonymous_variant	10/59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.805C>A	p.Arg269Arg	synonymous_variant	10/58	1		ENSP00000397885.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461282 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	12
DANN	Benign	0.70

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: rs886039392; hg19: chr3-4687362;