6-33649687-C-T

Variant names:

• chr6-33649687-C-T
• rs6457738
• NM_002224.4:c.161-6079C>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.161-6079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,076 control chromosomes in the GnomAD database, including 29,885 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 0.63 (29885 hom., cov: 33)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 16 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002224.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	NM_002224.4	MANE Select	c.161-6079C>T		intron	N/A	NP_002215.2	Q14573

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR3	ENST00000605930.3	TSL:1 MANE Select	c.161-6079C>T		intron	N/A	ENSP00000475177.1	Q14573
	ITPR3	ENST00000374316.9	TSL:5	c.161-6079C>T		intron	N/A	ENSP00000363435.4	Q14573
	ITPR3	ENST00000931640.1		c.161-6079C>T		intron	N/A	ENSP00000601699.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95211 AN: 151958 Hom.: 29862 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.627 AC: 95281 AN: 152076 Hom.: 29885 Cov.: 33 AF XY: 0.624 AC XY: 46400 AN XY: 74338

African (AFR) AF: 0.637 AC: 26404 AN: 41458

American (AMR) AF: 0.597 AC: 9125 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2218 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3496 AN: 5172

South Asian (SAS) AF: 0.603 AC: 2905 AN: 4820

European-Finnish (FIN) AF: 0.564 AC: 5964 AN: 10568

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 43032 AN: 67994

Other (OTH) AF: 0.676 AC: 1427 AN: 2110

Alfa AF: 0.633 Hom.: 107529

Bravo AF: 0.629

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.40
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: rs6457738; hg19: chr6-33617464;