rs6793265

Positions:

• chr3-4693849-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378452.1(ITPR1):​c.4281+108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,170,966 control chromosomes in the GnomAD database, including 7,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (783 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7155 hom.)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0440

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-4693849-C-T is Benign according to our data. Variant chr3-4693849-C-T is described in ClinVar as [Benign]. Clinvar id is 1258510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.4281+108C>T		intron_variant		ENST00000649015.2	NP_001365381.1
ITPR1	NM_001099952.4	c.4254+108C>T		intron_variant			NP_001093422.2
ITPR1	NM_001168272.2	c.4236+108C>T		intron_variant			NP_001161744.1
ITPR1	NM_002222.7	c.4209+108C>T		intron_variant			NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.4281+108C>T		intron_variant			NM_001378452.1	ENSP00000497605

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13585 AN: 152130 Hom.: 781 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0979

GnomAD4 exome AF: 0.115 AC: 117035 AN: 1018718 Hom.: 7155 AF XY: 0.115 AC XY: 58021 AN XY: 502792

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0957

Gnomad4 EAS exome AF: 0.0103

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0894 AC: 13604 AN: 152248 Hom.: 783 Cov.: 33 AF XY: 0.0879 AC XY: 6547 AN XY: 74448

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0997

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.100

Alfa AF: 0.115 Hom.: 481

Bravo AF: 0.0883

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
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

LitVar

Other links and lift over

dbSNP: rs6793265; hg19: chr3-4735533;