chr3-4814520-C-T

Position:

• chr3-4814520-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001378452.1(ITPR1):​c.7659C>T​(p.Ser2553Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,558,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.188

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 3-4814520-C-T is Benign according to our data. Variant chr3-4814520-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 447600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.188 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.7659C>T	p.Ser2553Ser	synonymous_variant	58/62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.7659C>T	p.Ser2553Ser	synonymous_variant	58/62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.7635C>T	p.Ser2545Ser	synonymous_variant	58/62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.7632C>T	p.Ser2544Ser	synonymous_variant	58/62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.7617C>T	p.Ser2539Ser	synonymous_variant	57/61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.7614C>T	p.Ser2538Ser	synonymous_variant	57/61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.7587C>T	p.Ser2529Ser	synonymous_variant	55/59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.7515C>T	p.Ser2505Ser	synonymous_variant	55/59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.7470C>T	p.Ser2490Ser	synonymous_variant	54/58	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.5421C>T	p.Ser1807Ser	synonymous_variant	38/42			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.4836C>T	p.Ser1612Ser	synonymous_variant	35/39			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.4599C>T	p.Ser1533Ser	synonymous_variant	35/39			ENSP00000498022.1

Frequencies

GnomAD3 genomes AF: 0.0000488 AC: 6 AN: 123004 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000836

Gnomad SAS AF: 0.000274

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000442 AC: 11 AN: 249102 Hom.: 0 AF XY: 0.0000296 AC XY: 4 AN XY: 135120

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000501

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000181 AC: 26 AN: 1435944 Hom.: 0 Cov.: 38 AF XY: 0.0000182 AC XY: 13 AN XY: 714062

Gnomad4 AFR exome AF: 0.0000310

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000236

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000913

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000488 AC: 6 AN: 123052 Hom.: 0 Cov.: 27 AF XY: 0.0000348 AC XY: 2 AN XY: 57448

Gnomad4 AFR AF: 0.0000620

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000837

Gnomad4 SAS AF: 0.000274

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000420 Hom.: 1

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 02, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 23, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	12
DANN	Benign	0.97

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: rs200562410; hg19: chr3-4856204; COSMIC: COSV57002869; COSMIC: COSV57002869;