rs373127487

Variant names:

• chr3-4710336-C-A
• NM_001378452.1:c.4854C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-4710336-C-A
• chr3-4710336-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378452.1(ITPR1):​c.4854C>A​(p.Ser1618Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,152 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. S1618S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.35

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]

LOC124906210 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-4.35 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.4854C>A	p.Ser1618Ser	synonymous_variant	Exon 38 of 62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.4854C>A	p.Ser1618Ser	synonymous_variant	Exon 38 of 62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.4827C>A	p.Ser1609Ser	synonymous_variant	Exon 38 of 62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.4827C>A	p.Ser1609Ser	synonymous_variant	Exon 38 of 62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.4809C>A	p.Ser1603Ser	synonymous_variant	Exon 37 of 61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.4809C>A	p.Ser1603Ser	synonymous_variant	Exon 37 of 61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.4782C>A	p.Ser1594Ser	synonymous_variant	Exon 35 of 59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.4827C>A	p.Ser1609Ser	synonymous_variant	Exon 38 of 59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.4782C>A	p.Ser1594Ser	synonymous_variant	Exon 37 of 58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.2664C>A	p.Ser888Ser	synonymous_variant	Exon 19 of 42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.2154C>A	p.Ser718Ser	synonymous_variant	Exon 16 of 39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.1761C>A	p.Ser587Ser	synonymous_variant	Exon 14 of 39			ENSP00000498022.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408152 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 694764

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

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	-0.67
CADD	Benign	0.16
DANN	Benign	0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-4752020;