chr3-4700592-A-G

Position:

• chr3-4700592-A-G

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.4536+651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,998 control chromosomes in the GnomAD database, including 11,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11381 hom., cov: 31)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.400

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-4700592-A-G is Benign according to our data. Variant chr3-4700592-A-G is described in ClinVar as [Benign]. Clinvar id is 225778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.4536+651A>G		intron_variant		ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.4491+651A>G		intron_variant			NP_001161744.1
ITPR1	NM_001099952.4	c.4509+651A>G		intron_variant			NP_001093422.2
ITPR1	NM_002222.7	c.4464+651A>G		intron_variant			NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.4536+651A>G		intron_variant			NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.4509+651A>G		intron_variant		5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.4509+651A>G		intron_variant				ENSP00000498014.1
ITPR1	ENST00000650294.1	c.4491+651A>G		intron_variant				ENSP00000498056.1
ITPR1	ENST00000443694.5	c.4491+651A>G		intron_variant		1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.4464+651A>G		intron_variant				ENSP00000497026.1
ITPR1	ENST00000357086.10	c.4509+651A>G		intron_variant		1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.4464+651A>G		intron_variant		1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.2346+651A>G		intron_variant				ENSP00000497872.1
ITPR1	ENST00000648431.1	c.1836+651A>G		intron_variant				ENSP00000498149.1
ITPR1	ENST00000648212.1	c.1443+651A>G		intron_variant				ENSP00000498022.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56875 AN: 151880 Hom.: 11367 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.316

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 56948 AN: 151998 Hom.: 11381 Cov.: 31 AF XY: 0.368 AC XY: 27381 AN XY: 74306

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0817

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.315

Alfa AF: 0.369 Hom.: 6366

Bravo AF: 0.370

Asia WGS AF: 0.137 AC: 479 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.79

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: rs6762644; hg19: chr3-4742276;