6-33664237-A-G

Variant names:

• chr6-33664237-A-G
• rs1536036
• NM_002224.4:c.1148+357A>G

Variant summary

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

The NM_002224.4(ITPR3):​c.1148+357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,910 control chromosomes in the GnomAD database, including 21,115 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 0.53 (21115 hom., cov: 30)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 12 publications found

Genes affected

ITPR3 (HGNC:6182): (inositol 1,4,5-trisphosphate receptor type 3) This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth. [provided by RefSeq, Aug 2010]

ITPR3 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease, demyelinating, type 1J

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.1148+357A>G		intron_variant	Intron 11 of 57	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.1148+357A>G		intron_variant	Intron 11 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.1148+357A>G		intron_variant	Intron 12 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79928 AN: 151792 Hom.: 21108 Cov.: 30

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.526 AC: 79970 AN: 151910 Hom.: 21115 Cov.: 30 AF XY: 0.523 AC XY: 38863 AN XY: 74242

African (AFR) AF: 0.540 AC: 22349 AN: 41408

American (AMR) AF: 0.544 AC: 8308 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2287 AN: 3466

East Asian (EAS) AF: 0.354 AC: 1821 AN: 5142

South Asian (SAS) AF: 0.421 AC: 2022 AN: 4804

European-Finnish (FIN) AF: 0.520 AC: 5493 AN: 10564

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36034 AN: 67940

Other (OTH) AF: 0.518 AC: 1095 AN: 2114

Alfa AF: 0.527 Hom.: 95838

Bravo AF: 0.530

Asia WGS AF: 0.373 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.53
PhyloP100		0.38
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: rs1536036; hg19: chr6-33632014;