chr6-33637241-G-A

Variant names:

• chr6-33637241-G-A
• rs10947418
• NM_002224.4:c.90-3243G>A

Variant summary

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

The NM_002224.4(ITPR3):​c.90-3243G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,064 control chromosomes in the GnomAD database, including 1,846 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 0.13 (1846 hom., cov: 31)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.90-3243G>A		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.90-3243G>A		intron_variant	Intron 1 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.90-3243G>A		intron_variant	Intron 2 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20453 AN: 151948 Hom.: 1844 Cov.: 31

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0557

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.135 AC: 20462 AN: 152064 Hom.: 1846 Cov.: 31 AF XY: 0.130 AC XY: 9661 AN XY: 74342

African (AFR) AF: 0.0345 AC: 1431 AN: 41514

American (AMR) AF: 0.168 AC: 2574 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3466

East Asian (EAS) AF: 0.0556 AC: 288 AN: 5176

South Asian (SAS) AF: 0.0731 AC: 350 AN: 4790

European-Finnish (FIN) AF: 0.141 AC: 1492 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13030 AN: 67946

Other (OTH) AF: 0.156 AC: 329 AN: 2104

Alfa AF: 0.178 Hom.: 1166

Bravo AF: 0.135

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.39
PhyloP100		0.76
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: rs10947418; hg19: chr6-33605018;