chr7-130380535-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001868.4(CPA1):c.15G>A(p.Leu5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000836 in 1,316,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CPA1
NM_001868.4 synonymous
NM_001868.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.09
Genes affected
CPA1 (HGNC:2296): (carboxypeptidase A1) This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. This enzyme is produced in the pancreas and preferentially cleaves C-terminal branched-chain and aromatic amino acids from dietary proteins. This gene and several family members are present in a gene cluster on chromosome 7. Mutations in this gene may be linked to chronic pancreatitis, while elevated protein levels may be associated with pancreatic cancer. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
Synonymous conserved (PhyloP=1.09 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPA1 | NM_001868.4 | c.15G>A | p.Leu5= | synonymous_variant | 1/10 | ENST00000011292.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPA1 | ENST00000011292.8 | c.15G>A | p.Leu5= | synonymous_variant | 1/10 | 1 | NM_001868.4 | P1 | |
CPA1 | ENST00000604896.5 | c.15G>A | p.Leu5= | synonymous_variant | 1/6 | 3 | |||
CPA1 | ENST00000481342.5 | c.-200+126G>A | intron_variant | 3 | |||||
CPA1 | ENST00000491460.5 | n.42G>A | non_coding_transcript_exon_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000826 AC: 1AN: 121018Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 64682
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GnomAD4 exome AF: 0.00000344 AC: 4AN: 1164236Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 557872
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary pancreatitis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2021 | The c.15G>A variant (also known as p.L5L) is located in coding exon 1 of the CPA1 gene. This variant results from a G to A substitution at nucleotide position 15. This nucleotide substitution does not change the leucine at codon 5. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at