rs41304179

Variant names:

• chr3-4710317-C-G
• rs41304179
• NM_001378452.1:c.4843-8C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-4710317-C-G
• chr3-4710317-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001378452.1(ITPR1):​c.4843-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 splice_region, intron
• Scores: Splicing: ADA: 0.00009699
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• aniridia-cerebellar ataxia-intellectual disability syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• spinocerebellar ataxia type 29

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
• spinocerebellar ataxia type 15/16

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

LOC124906210 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-4710317-C-G is Benign according to our data. Variant chr3-4710317-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3004193.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.4843-8C>G		splice_region_variant, intron_variant	Intron 37 of 61	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.4843-8C>G		splice_region_variant, intron_variant	Intron 37 of 61		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.4816-8C>G		splice_region_variant, intron_variant	Intron 37 of 61	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.4816-8C>G		splice_region_variant, intron_variant	Intron 37 of 61			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.4798-8C>G		splice_region_variant, intron_variant	Intron 36 of 60			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.4798-8C>G		splice_region_variant, intron_variant	Intron 36 of 60	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.4771-8C>G		splice_region_variant, intron_variant	Intron 34 of 58			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.4816-8C>G		splice_region_variant, intron_variant	Intron 37 of 58	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.4771-8C>G		splice_region_variant, intron_variant	Intron 36 of 57	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.2653-8C>G		splice_region_variant, intron_variant	Intron 18 of 41			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.2143-8C>G		splice_region_variant, intron_variant	Intron 15 of 38			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.1750-8C>G		splice_region_variant, intron_variant	Intron 13 of 38			ENSP00000498022.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383724 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 679370

African (AFR) AF: 0.00 AC: 0 AN: 31582

American (AMR) AF: 0.00 AC: 0 AN: 35654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24474

East Asian (EAS) AF: 0.00 AC: 0 AN: 36520

South Asian (SAS) AF: 0.00 AC: 0 AN: 77882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065808

Other (OTH) AF: 0.0000175 AC: 1 AN: 57088

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.77
DANN	Benign	0.40
PhyloP100		-0.027

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000097
dbscSNV1_RF	Benign	0.028
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

Other links and lift over

dbSNP: rs41304179; hg19: chr3-4752001;