Genetic Variant ITPR3:c.283-108delT (chr6-33657823-GT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002224.4(ITPR3):c.283-108delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 815,184 control chromosomes in the GnomAD database, including 55,051 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 10353 hom., cov: 0)

Exomes 𝑓: 0.35 ( 44698 hom. )

Consequence

ITPR3
NM_002224.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

Publications

2 publications found

Variant links:

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

ITPR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 6-33657823-GT-G is Benign according to our data. Variant chr6-33657823-GT-G is described in ClinVar as [Benign]. Clinvar id is 1247934.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4 link	c.283-108delT		intron_variant	Intron 3 of 57	ENST00000605930.3	NP_002215.2	Q14573A6H8K3Q59ES2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3 link	c.283-108delT		intron_variant	Intron 3 of 57	1	NM_002224.4	ENSP00000475177.1		Q14573
ITPR3	ENST00000374316.9 link	c.283-108delT		intron_variant	Intron 4 of 58	5		ENSP00000363435.4		Q14573

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

54990

AN:

151416

Hom.:

10336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.350

AC:

232509

AN:

663650

Hom.:

44698

AF XY:

0.358

AC XY:

125104

AN XY:

349884

show subpopulations

African (AFR)

AF:

0.451

AC:

7890

AN:

17484

American (AMR)

AF:

0.284

AC:

9582

AN:

33690

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

5331

AN:

19350

East Asian (EAS)

AF:

0.465

AC:

14378

AN:

30946

South Asian (SAS)

AF:

0.522

AC:

33341

AN:

63906

European-Finnish (FIN)

AF:

0.376

AC:

14888

AN:

39556

Middle Eastern (MID)

AF:

0.318

AC:

1289

AN:

4052

European-Non Finnish (NFE)

AF:

0.318

AC:

134177

AN:

421494

Other (OTH)

AF:

0.351

AC:

11633

AN:

33172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

7257

14515

21772

29030

36287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.363

AC:

55037

AN:

151534

Hom.:

10353

Cov.:

AF XY:

0.367

AC XY:

27169

AN XY:

74016

show subpopulations

African (AFR)

AF:

0.437

AC:

18029

AN:

41278

American (AMR)

AF:

0.309

AC:

4711

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

981

AN:

3466

East Asian (EAS)

AF:

0.480

AC:

2454

AN:

5110

South Asian (SAS)

AF:

0.522

AC:

2486

AN:

4764

European-Finnish (FIN)

AF:

0.367

AC:

3862

AN:

10532

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21392

AN:

67832

Other (OTH)

AF:

0.337

AC:

710

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1733

3466

5200

6933

8666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.167

Hom.:

305

Bravo

AF:

0.359

Asia WGS

AF:

0.541

AC:

1879

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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6-33657823-GT-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over