chr6-33640602-T-C

Position:

• chr6-33640602-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002224.4(ITPR3):​c.160+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 1,503,214 control chromosomes in the GnomAD database, including 733,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (71666 hom., cov: 32)
  • Exomes 𝑓: 0.99 (661565 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.713

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 6-33640602-T-C is Benign according to our data. Variant chr6-33640602-T-C is described in ClinVar as [Benign]. Clinvar id is 1220735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.160+48T>C		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.160+48T>C		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.160+48T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147543 AN: 152140 Hom.: 71613 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.965

GnomAD3 exomes AF: 0.985 AC: 206201 AN: 209352 Hom.: 101601 AF XY: 0.986 AC XY: 110802 AN XY: 112336

Gnomad AFR exome AF: 0.918

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.979

Gnomad EAS exome AF: 0.998

Gnomad SAS exome AF: 0.990

Gnomad FIN exome AF: 0.998

Gnomad NFE exome AF: 0.990

Gnomad OTH exome AF: 0.986

GnomAD4 exome AF: 0.990 AC: 1336836 AN: 1350956 Hom.: 661565 Cov.: 19 AF XY: 0.990 AC XY: 665999 AN XY: 673024

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.977

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.989

Gnomad4 FIN exome AF: 0.997

Gnomad4 NFE exome AF: 0.992

Gnomad4 OTH exome AF: 0.985

GnomAD4 genome AF: 0.970 AC: 147655 AN: 152258 Hom.: 71666 Cov.: 32 AF XY: 0.972 AC XY: 72340 AN XY: 74438

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.990

Gnomad4 OTH AF: 0.965

Alfa AF: 0.984 Hom.: 82655

Bravo AF: 0.965

Asia WGS AF: 0.990 AC: 3443 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs4713647; hg19: chr6-33608379;