rs2281919

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002224.4(ITPR3):​c.7947+309A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 556,010 control chromosomes in the GnomAD database, including 8,430 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 0.15 ( 2055 hom., cov: 33)
Exomes 𝑓: 0.17 ( 6375 hom. )

Consequence

ITPR3
NM_002224.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.173
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]
UQCC2 (HGNC:21237): (ubiquinol-cytochrome c reductase complex assembly factor 2) This gene encodes a nucleoid protein localized to the mitochondria inner membrane. The encoded protein affects regulation of insulin secretion, mitochondrial ATP production, and myogenesis through modulation of mitochondrial respiratory chain activity. [provided by RefSeq, Oct 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITPR3NM_002224.4 linkuse as main transcriptc.7947+309A>C intron_variant ENST00000605930.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITPR3ENST00000605930.3 linkuse as main transcriptc.7947+309A>C intron_variant 1 NM_002224.4 P1
UQCC2ENST00000374231.8 linkuse as main transcriptc.*85T>G 3_prime_UTR_variant 5/53
ITPR3ENST00000374316.9 linkuse as main transcriptc.7947+309A>C intron_variant 5 P1
UQCC2ENST00000606961.1 linkuse as main transcriptn.3264T>G non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.150
AC:
22872
AN:
152126
Hom.:
2054
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0843
Gnomad AMI
AF:
0.121
Gnomad AMR
AF:
0.174
Gnomad ASJ
AF:
0.212
Gnomad EAS
AF:
0.0458
Gnomad SAS
AF:
0.0704
Gnomad FIN
AF:
0.133
Gnomad MID
AF:
0.218
Gnomad NFE
AF:
0.198
Gnomad OTH
AF:
0.181
GnomAD3 exomes
AF:
0.146
AC:
7043
AN:
48332
Hom.:
652
AF XY:
0.142
AC XY:
3506
AN XY:
24668
show subpopulations
Gnomad AFR exome
AF:
0.0817
Gnomad AMR exome
AF:
0.163
Gnomad ASJ exome
AF:
0.240
Gnomad EAS exome
AF:
0.0407
Gnomad SAS exome
AF:
0.0762
Gnomad FIN exome
AF:
0.101
Gnomad NFE exome
AF:
0.205
Gnomad OTH exome
AF:
0.180
GnomAD4 exome
AF:
0.169
AC:
68173
AN:
403766
Hom.:
6375
Cov.:
2
AF XY:
0.165
AC XY:
34754
AN XY:
210674
show subpopulations
Gnomad4 AFR exome
AF:
0.0826
Gnomad4 AMR exome
AF:
0.161
Gnomad4 ASJ exome
AF:
0.227
Gnomad4 EAS exome
AF:
0.0892
Gnomad4 SAS exome
AF:
0.0771
Gnomad4 FIN exome
AF:
0.135
Gnomad4 NFE exome
AF:
0.198
Gnomad4 OTH exome
AF:
0.170
GnomAD4 genome
AF:
0.150
AC:
22891
AN:
152244
Hom.:
2055
Cov.:
33
AF XY:
0.144
AC XY:
10728
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0844
Gnomad4 AMR
AF:
0.174
Gnomad4 ASJ
AF:
0.212
Gnomad4 EAS
AF:
0.0457
Gnomad4 SAS
AF:
0.0707
Gnomad4 FIN
AF:
0.133
Gnomad4 NFE
AF:
0.198
Gnomad4 OTH
AF:
0.178
Alfa
AF:
0.178
Hom.:
621
Bravo
AF:
0.153
Asia WGS
AF:
0.0690
AC:
240
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.8
DANN
Benign
0.82

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2281919; hg19: chr6-33663171; API