6-33627622-A-G

Variant names:

• chr6-33627622-A-G
• rs4711332
• NM_002224.4:c.89+5931A>G

Variant summary

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

The NM_002224.4(ITPR3):​c.89+5931A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,254 control chromosomes in the GnomAD database, including 56,376 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 0.86 (56376 hom., cov: 34)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 14 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.89+5931A>G		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.89+5931A>G		intron_variant	Intron 1 of 57	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.89+5931A>G		intron_variant	Intron 2 of 58	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130817 AN: 152136 Hom.: 56326 Cov.: 34

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.860 AC: 130923 AN: 152254 Hom.: 56376 Cov.: 34 AF XY: 0.866 AC XY: 64462 AN XY: 74446

African (AFR) AF: 0.838 AC: 34780 AN: 41518

American (AMR) AF: 0.880 AC: 13458 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3196 AN: 3470

East Asian (EAS) AF: 0.963 AC: 4999 AN: 5190

South Asian (SAS) AF: 0.900 AC: 4342 AN: 4826

European-Finnish (FIN) AF: 0.901 AC: 9558 AN: 10610

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57765 AN: 68034

Other (OTH) AF: 0.867 AC: 1830 AN: 2110

Alfa AF: 0.855 Hom.: 141629

Bravo AF: 0.857

Asia WGS AF: 0.912 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		-0.026
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: rs4711332; hg19: chr6-33595399;