chr7-130380556-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001868.4(CPA1):c.36G>A(p.Gly12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000858 in 1,164,900 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 Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000086 ( 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 Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 7-130380556-G-A is Benign according to our data. Variant chr7-130380556-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1673402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
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.36G>A | p.Gly12= | synonymous_variant | 1/10 | ENST00000011292.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPA1 | ENST00000011292.8 | c.36G>A | p.Gly12= | synonymous_variant | 1/10 | 1 | NM_001868.4 | P1 | |
CPA1 | ENST00000604896.5 | c.36G>A | p.Gly12= | synonymous_variant | 1/6 | 3 | |||
CPA1 | ENST00000481342.5 | c.-200+147G>A | intron_variant | 3 | |||||
CPA1 | ENST00000491460.5 | n.63G>A | non_coding_transcript_exon_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000827 AC: 1AN: 120908Hom.: 0 AF XY: 0.0000155 AC XY: 1AN XY: 64636
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GnomAD4 exome AF: 0.00000858 AC: 10AN: 1164900Hom.: 0 Cov.: 29 AF XY: 0.00000717 AC XY: 4AN XY: 557982
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary pancreatitis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2021 | - - |
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