NM_001378452.1:c.93-41T>G

Variant names:

• chr3-4520983-T-G
• rs1038639
• NM_001378452.1:c.93-41T>G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001378452.1(ITPR1):​c.93-41T>G variant causes a intron change. The variant allele was found at a frequency of 0.553 in 1,475,666 control chromosomes in the GnomAD database, including 235,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (18726 hom., cov: 32)
  • Exomes 𝑓: 0.56 (216691 hom.)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.22

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-4520983-T-G is Benign according to our data. Variant chr3-4520983-T-G is described in ClinVar as [Benign]. Clinvar id is 1293507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.93-41T>G		intron_variant	Intron 3 of 61	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.93-41T>G		intron_variant	Intron 3 of 60		NP_001161744.1
ITPR1	NM_001099952.4	c.93-41T>G		intron_variant	Intron 3 of 58		NP_001093422.2
ITPR1	NM_002222.7	c.93-41T>G		intron_variant	Intron 3 of 57		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.93-41T>G		intron_variant	Intron 3 of 61		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.93-41T>G		intron_variant	Intron 3 of 61	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.93-41T>G		intron_variant	Intron 3 of 61			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.93-41T>G		intron_variant	Intron 3 of 60			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.93-41T>G		intron_variant	Intron 3 of 60	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.93-41T>G		intron_variant	Intron 1 of 58			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.93-41T>G		intron_variant	Intron 3 of 58	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.93-41T>G		intron_variant	Intron 3 of 57	1		ENSP00000397885.2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68817 AN: 152000 Hom.: 18719 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.514

GnomAD3 exomes AF: 0.558 AC: 136815 AN: 245052 Hom.: 40459 AF XY: 0.576 AC XY: 76527 AN XY: 132868

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.723

Gnomad SAS exome AF: 0.725

Gnomad FIN exome AF: 0.503

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.584

GnomAD4 exome AF: 0.564 AC: 746697 AN: 1323548 Hom.: 216691 Cov.: 19 AF XY: 0.572 AC XY: 380895 AN XY: 666058

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.478

Gnomad4 ASJ exome AF: 0.642

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.499

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.452 AC: 68824 AN: 152118 Hom.: 18726 Cov.: 32 AF XY: 0.458 AC XY: 34041 AN XY: 74362

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.516

Alfa AF: 0.564 Hom.: 37068

Bravo AF: 0.434

Asia WGS AF: 0.685 AC: 2380 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: 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	-0.42
CADD	Benign	12
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: rs1038639; hg19: chr3-4562667;