3-4837700-G-T

Variant names:

• chr3-4837700-G-T
• rs6779719
• NM_001378452.1:c.8190+765G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378452.1(ITPR1):​c.8190+765G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,082 control chromosomes in the GnomAD database, including 61,101 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 0.88 (61101 hom., cov: 30)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944
• Publications: 0 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)

ENSG00000235978 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378452.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR1	NM_001378452.1	MANE Select	c.8190+765G>T		intron	N/A	NP_001365381.1
	ITPR1	NM_001168272.2		c.8145+765G>T		intron	N/A	NP_001161744.1
	ITPR1	NM_001099952.4		c.8046+765G>T		intron	N/A	NP_001093422.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR1	ENST00000649015.2	MANE Select	c.8190+765G>T		intron	N/A	ENSP00000497605.1
	ITPR1	ENST00000354582.12	TSL:5	c.8166+765G>T		intron	N/A	ENSP00000346595.8
	ITPR1	ENST00000648266.1		c.8163+765G>T		intron	N/A	ENSP00000498014.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133451 AN: 151964 Hom.: 61092 Cov.: 30

Gnomad AFR AF: 0.586

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.878 AC: 133501 AN: 152082 Hom.: 61101 Cov.: 30 AF XY: 0.882 AC XY: 65579 AN XY: 74354

African (AFR) AF: 0.586 AC: 24253 AN: 41416

American (AMR) AF: 0.950 AC: 14532 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3358 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5161 AN: 5162

South Asian (SAS) AF: 0.995 AC: 4774 AN: 4796

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67722 AN: 67996

Other (OTH) AF: 0.899 AC: 1903 AN: 2116

Alfa AF: 0.899 Hom.: 8393

Bravo AF: 0.861

Asia WGS AF: 0.959 AC: 3335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.45
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6779719; hg19: chr3-4879384;