3-4693543-C-T

Position:

• chr3-4693543-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001378452.1(ITPR1):​c.4083C>T​(p.Phe1361Phe) 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 152,160 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=3.39 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.4083C>T	p.Phe1361Phe	synonymous_variant	33/62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.4038C>T	p.Phe1346Phe	synonymous_variant	32/61		NP_001161744.1
ITPR1	NM_001099952.4	c.4056C>T	p.Phe1352Phe	synonymous_variant	33/59		NP_001093422.2
ITPR1	NM_002222.7	c.4011C>T	p.Phe1337Phe	synonymous_variant	32/58		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.4083C>T	p.Phe1361Phe	synonymous_variant	33/62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.4056C>T	p.Phe1352Phe	synonymous_variant	33/62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.4056C>T	p.Phe1352Phe	synonymous_variant	33/62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.4038C>T	p.Phe1346Phe	synonymous_variant	32/61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.4038C>T	p.Phe1346Phe	synonymous_variant	32/61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.4011C>T	p.Phe1337Phe	synonymous_variant	30/59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.4056C>T	p.Phe1352Phe	synonymous_variant	33/59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.4011C>T	p.Phe1337Phe	synonymous_variant	32/58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.1893C>T	p.Phe631Phe	synonymous_variant	14/42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.1383C>T	p.Phe461Phe	synonymous_variant	11/39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.990C>T	p.Phe330Phe	synonymous_variant	9/39			ENSP00000498022.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74332

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs763239856; hg19: chr3-4735227;