rs304039

Variant names:

• chr3-4510742-T-G
• rs304039
• NM_001378452.1:c.-16-5734T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378452.1(ITPR1):​c.-16-5734T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,908 control chromosomes in the GnomAD database, including 9,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9002 hom., cov: 32)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.-16-5734T>G		intron_variant	Intron 2 of 61	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.-16-5734T>G		intron_variant	Intron 2 of 60		NP_001161744.1
ITPR1	NM_001099952.4	c.-16-5734T>G		intron_variant	Intron 2 of 58		NP_001093422.2
ITPR1	NM_002222.7	c.-16-5734T>G		intron_variant	Intron 2 of 57		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.-16-5734T>G		intron_variant	Intron 2 of 61		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.-16-5734T>G		intron_variant	Intron 2 of 61	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.-16-5734T>G		intron_variant	Intron 2 of 61			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.-16-5734T>G		intron_variant	Intron 2 of 60			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.-16-5734T>G		intron_variant	Intron 2 of 60	1		ENSP00000401671.2
ITPR1	ENST00000357086.10	c.-16-5734T>G		intron_variant	Intron 2 of 58	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.-16-5734T>G		intron_variant	Intron 2 of 57	1		ENSP00000397885.2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51481 AN: 151790 Hom.: 8993 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.339 AC: 51518 AN: 151908 Hom.: 9002 Cov.: 32 AF XY: 0.335 AC XY: 24850 AN XY: 74250

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.323

Alfa AF: 0.374 Hom.: 4752

Bravo AF: 0.343

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.85

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: rs304039; hg19: chr3-4552426;