dbSNP rs565843811: ITPR1:c.-341A>C (chr3-4493357-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001378452.1(ITPR1):c.-341A>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000198 in 151,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITPR1
NM_001378452.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.18

Variant links:

Genes affected

ITPR1 (HGNC:6180): (inositol 1,4,5-trisphosphate receptor type 1) This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

ITPR1 links:

ITPR1-DT (HGNC:44470): (ITPR1 divergent transcript)

ITPR1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.15).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1 link	c.-341A>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001378452.1 link	c.-341A>C		5_prime_UTR_variant	Exon 1 of 62	ENST00000649015.2	NP_001365381.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITPR1	ENST00000649015 link	c.-341A>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 62		NM_001378452.1	ENSP00000497605.1	Q14643-1
ITPR1	ENST00000354582 link	c.-341A>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 62	5		ENSP00000346595.8	A0A3F2YNW8
ITPR1	ENST00000357086 link	c.-341A>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 59	1		ENSP00000349597.4	Q14643-3
ITPR1	ENST00000649015 link	c.-341A>C	5_prime_UTR_variant	Exon 1 of 62		NM_001378452.1	ENSP00000497605.1	Q14643-1
ITPR1	ENST00000354582 link	c.-341A>C	5_prime_UTR_variant	Exon 1 of 62	5		ENSP00000346595.8	A0A3F2YNW8
ITPR1	ENST00000357086 link	c.-341A>C	5_prime_UTR_variant	Exon 1 of 59	1		ENSP00000349597.4	Q14643-3
ITPR1	ENST00000648266.1 link	c.-341A>C	upstream_gene_variant				ENSP00000498014.1	A0A3B3IU04
ITPR1	ENST00000650294.1 link	c.-341A>C	upstream_gene_variant				ENSP00000498056.1	A0A3B3ITU8
ITPR1	ENST00000443694.5 link	c.-341A>C	upstream_gene_variant		1		ENSP00000401671.2	Q14643-2
ITPR1	ENST00000456211.8 link	c.-341A>C	upstream_gene_variant		1		ENSP00000397885.2	Q14643-4

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1964

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

1062

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.96

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over