rs6901411

Variant names:

• chr6-33665750-A-G
• rs6901411
• NM_002224.4:c.1410-85A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002224.4(ITPR3):​c.1410-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,488,066 control chromosomes in the GnomAD database, including 66,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4951 hom., cov: 32)
  • Exomes 𝑓: 0.30 (61109 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.667
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-33665750-A-G is Benign according to our data. Variant chr6-33665750-A-G is described in ClinVar as Benign. ClinVar VariationId is 1293549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.1410-85A>G		intron_variant	Intron 13 of 57	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.1410-85A>G		intron_variant	Intron 13 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.1410-85A>G		intron_variant	Intron 14 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36794 AN: 151866 Hom.: 4948 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.296 AC: 395953 AN: 1336082 Hom.: 61109 AF XY: 0.300 AC XY: 198898 AN XY: 663932

African (AFR) AF: 0.129 AC: 4015 AN: 31050

American (AMR) AF: 0.243 AC: 10381 AN: 42668

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4116 AN: 23814

East Asian (EAS) AF: 0.437 AC: 16798 AN: 38414

South Asian (SAS) AF: 0.399 AC: 31760 AN: 79642

European-Finnish (FIN) AF: 0.303 AC: 15422 AN: 50964

Middle Eastern (MID) AF: 0.214 AC: 1148 AN: 5376

European-Non Finnish (NFE) AF: 0.294 AC: 296399 AN: 1008344

Other (OTH) AF: 0.285 AC: 15914 AN: 55810

GnomAD4 genome AF: 0.242 AC: 36819 AN: 151984 Hom.: 4951 Cov.: 32 AF XY: 0.247 AC XY: 18326 AN XY: 74278

African (AFR) AF: 0.133 AC: 5530 AN: 41452

American (AMR) AF: 0.235 AC: 3590 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3464

East Asian (EAS) AF: 0.438 AC: 2248 AN: 5132

South Asian (SAS) AF: 0.401 AC: 1928 AN: 4808

European-Finnish (FIN) AF: 0.292 AC: 3096 AN: 10590

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18981 AN: 67946

Other (OTH) AF: 0.230 AC: 487 AN: 2114

Alfa AF: 0.262 Hom.: 5414

Bravo AF: 0.232

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.67
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: rs6901411; hg19: chr6-33633527; COSMIC: COSV65412842;