7-130380524-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001868.4(CPA1):c.4C>T(p.Arg2Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000837 in 1,314,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2Q) has been classified as Likely benign.
Frequency
Consequence
NM_001868.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CPA1 | ENST00000011292.8 | c.4C>T | p.Arg2Trp | missense_variant | Exon 1 of 10 | 1 | NM_001868.4 | ENSP00000011292.3 | ||
CPA1 | ENST00000604896.5 | c.4C>T | p.Arg2Trp | missense_variant | Exon 1 of 6 | 3 | ENSP00000475021.2 | |||
CPA1 | ENST00000481342.5 | c.-200+115C>T | intron_variant | Intron 1 of 4 | 3 | ENSP00000420218.1 | ||||
CPA1 | ENST00000491460.5 | n.31C>T | non_coding_transcript_exon_variant | Exon 1 of 6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000774 AC: 9AN: 1162508Hom.: 0 Cov.: 29 AF XY: 0.00000898 AC XY: 5AN XY: 556958
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
Hereditary pancreatitis Uncertain:1
The p.R2W variant (also known as c.4C>T), located in coding exon 1 of the CPA1 gene, results from a C to T substitution at nucleotide position 4. The arginine at codon 2 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2 of the CPA1 protein (p.Arg2Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CPA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1000164). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at