dbSNP rs78064999: ITPR3:c.161-34T>C (chr6-33655732-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002224.4(ITPR3):c.161-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 1,613,086 control chromosomes in the GnomAD database, including 2,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 222 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1841 hom. )

Consequence

ITPR3
NM_002224.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.323

Publications

6 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 6-33655732-T-C is Benign according to our data. Variant chr6-33655732-T-C is described in ClinVar as [Benign]. Clinvar id is 1270368.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4 link	c.161-34T>C		intron_variant	Intron 2 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.161-34T>C		intron_variant	Intron 2 of 57	1	NM_002224.4	ENSP00000475177.1		Q14573
ITPR3	ENST00000374316.9 link	c.161-34T>C		intron_variant	Intron 3 of 58	5		ENSP00000363435.4		Q14573

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7550

AN:

152034

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0698

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0383

Gnomad ASJ

AF:

0.0439

Gnomad EAS

AF:

0.00828

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0507

Gnomad OTH

AF:

0.0511

GnomAD2 exomes

AF:

0.0371

AC:

9257

AN:

249548

AF XY:

0.0356

show subpopulations

Gnomad AFR exome

AF:

0.0683

Gnomad AMR exome

AF:

0.0249

Gnomad ASJ exome

AF:

0.0434

Gnomad EAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0405

GnomAD4 exome

AF:

0.0468

AC:

68311

AN:

1460934

Hom.:

1841

Cov.:

AF XY:

0.0453

AC XY:

32895

AN XY:

726688

show subpopulations

African (AFR)

AF:

0.0660

AC:

2210

AN:

33466

American (AMR)

AF:

0.0283

AC:

1265

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0411

AC:

1074

AN:

26100

East Asian (EAS)

AF:

0.00695

AC:

276

AN:

39684

South Asian (SAS)

AF:

0.0145

AC:

1252

AN:

86208

European-Finnish (FIN)

AF:

0.0212

AC:

1131

AN:

53284

Middle Eastern (MID)

AF:

0.0463

AC:

266

AN:

5746

European-Non Finnish (NFE)

AF:

0.0524

AC:

58220

AN:

1111428

Other (OTH)

AF:

0.0434

AC:

2617

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2956

5911

8867

11822

14778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0498

AC:

7573

AN:

152152

Hom.:

222

Cov.:

AF XY:

0.0478

AC XY:

3554

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0702

AC:

2911

AN:

41488

American (AMR)

AF:

0.0383

AC:

585

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0439

AC:

152

AN:

3466

East Asian (EAS)

AF:

0.00830

AC:

AN:

5182

South Asian (SAS)

AF:

0.0139

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0199

AC:

211

AN:

10590

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0507

AC:

3449

AN:

67998

Other (OTH)

AF:

0.0506

AC:

107

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

365

731

1096

1462

1827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0494

Hom.:

Bravo

AF:

0.0527

Asia WGS

AF:

0.0140

AC:

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

8.2

(source)

DANN

Benign

0.51

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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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rs78064999

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