chr6-33638746-C-T

Variant names:

• chr6-33638746-C-T
• rs4713646
• NM_002224.4:c.90-1738C>T

Variant summary

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

The NM_002224.4(ITPR3):​c.90-1738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,028 control chromosomes in the GnomAD database, including 6,684 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 0.29 (6684 hom., cov: 33)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 20 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.90-1738C>T		intron_variant	Intron 1 of 57	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.90-1738C>T		intron_variant	Intron 1 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.90-1738C>T		intron_variant	Intron 2 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43371 AN: 151910 Hom.: 6680 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.285 AC: 43401 AN: 152028 Hom.: 6684 Cov.: 33 AF XY: 0.285 AC XY: 21162 AN XY: 74330

African (AFR) AF: 0.367 AC: 15189 AN: 41418

American (AMR) AF: 0.243 AC: 3719 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2455 AN: 5156

South Asian (SAS) AF: 0.441 AC: 2124 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1880 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16322 AN: 67974

Other (OTH) AF: 0.291 AC: 615 AN: 2112

Alfa AF: 0.273 Hom.: 7519

Bravo AF: 0.288

Asia WGS AF: 0.484 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.47
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: rs4713646; hg19: chr6-33606523;