6-33655156-C-T

Variant names:

• chr6-33655156-C-T
• rs1570760
• NM_002224.4:c.161-610C>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.161-610C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,102 control chromosomes in the GnomAD database, including 3,754 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 0.20 (3754 hom., cov: 32)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.161-610C>T		intron_variant	Intron 2 of 57	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.161-610C>T		intron_variant	Intron 2 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.161-610C>T		intron_variant	Intron 3 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30717 AN: 151984 Hom.: 3757 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.202 AC: 30712 AN: 152102 Hom.: 3754 Cov.: 32 AF XY: 0.210 AC XY: 15607 AN XY: 74334

African (AFR) AF: 0.0628 AC: 2607 AN: 41532

American (AMR) AF: 0.254 AC: 3879 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 984 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1449 AN: 5166

South Asian (SAS) AF: 0.293 AC: 1411 AN: 4812

European-Finnish (FIN) AF: 0.351 AC: 3702 AN: 10556

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.236 AC: 16035 AN: 67986

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.217 Hom.: 8567

Bravo AF: 0.188

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.26
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1570760; hg19: chr6-33622933;