3-4516490-A-G
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1
The NM_001378452.1(ITPR1):c.-2A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,551,514 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001378452.1 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 62 | ENST00000649015.2 | NP_001365381.1 | ||
ITPR1 | NM_001168272.2 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 61 | NP_001161744.1 | |||
ITPR1 | NM_001099952.4 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 59 | NP_001093422.2 | |||
ITPR1 | NM_002222.7 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 58 | NP_002213.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 62 | NM_001378452.1 | ENSP00000497605.1 | ||||
ITPR1 | ENST00000354582 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 62 | 5 | ENSP00000346595.8 | ||||
ITPR1 | ENST00000648266 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 62 | ENSP00000498014.1 | |||||
ITPR1 | ENST00000650294 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 61 | ENSP00000498056.1 | |||||
ITPR1 | ENST00000443694 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 61 | 1 | ENSP00000401671.2 | ||||
ITPR1 | ENST00000648309 | c.-2A>G | 5_prime_UTR_variant | Exon 1 of 59 | ENSP00000497026.1 | |||||
ITPR1 | ENST00000357086 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 59 | 1 | ENSP00000349597.4 | ||||
ITPR1 | ENST00000456211 | c.-2A>G | 5_prime_UTR_variant | Exon 3 of 58 | 1 | ENSP00000397885.2 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000419 AC: 93AN: 221952Hom.: 0 AF XY: 0.000338 AC XY: 41AN XY: 121216
GnomAD4 exome AF: 0.000392 AC: 549AN: 1399174Hom.: 1 Cov.: 25 AF XY: 0.000359 AC XY: 250AN XY: 696920
GnomAD4 genome AF: 0.000203 AC: 31AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:1
Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29758065) -
not specified Benign:1
- -
Autosomal dominant cerebellar ataxia Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at