3-4787891-T-C

Position:

• chr3-4787891-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378452.1(ITPR1):​c.6616-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,269,810 control chromosomes in the GnomAD database, including 9,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (643 hom., cov: 31)
  • Exomes 𝑓: 0.12 (8946 hom.)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-4787891-T-C is Benign according to our data. Variant chr3-4787891-T-C is described in ClinVar as [Benign]. Clinvar id is 1240984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR1	NM_001378452.1	c.6616-56T>C		intron_variant		ENST00000649015.2
ITPR1	NM_001099952.4	c.6472-56T>C		intron_variant
ITPR1	NM_001168272.2	c.6571-56T>C		intron_variant
ITPR1	NM_002222.7	c.6427-56T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR1	ENST00000649015.2	c.6616-56T>C		intron_variant			NM_001378452.1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12404 AN: 151686 Hom.: 644 Cov.: 31

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0874

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0846

GnomAD4 exome AF: 0.117 AC: 131215 AN: 1118006 Hom.: 8946 AF XY: 0.115 AC XY: 64700 AN XY: 564900

Gnomad4 AFR exome AF: 0.0199

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.000168

Gnomad4 SAS exome AF: 0.0328

Gnomad4 FIN exome AF: 0.0916

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0817 AC: 12402 AN: 151804 Hom.: 643 Cov.: 31 AF XY: 0.0779 AC XY: 5781 AN XY: 74168

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.0874

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.116 Hom.: 1476

Bravo AF: 0.0779

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.36

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: rs17786144; hg19: chr3-4829575;