rs1796390308

Variant names:

• chr7-130380524-CG-C
• rs1796390308
• NM_001868.4:c.9delG

Your query was ambiguous. Multiple possible variants found:

• chr7-130380524-CG-C
• chr7-130380524-CG-CGGG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001868.4(CPA1):​c.9delG​(p.Leu4CysfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000086 in 1,162,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G3G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: CPA1 NM_001868.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

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]

CPA1 Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA1	NM_001868.4	MANE Select	c.9delG	p.Leu4CysfsTer4	frameshift	Exon 1 of 10	NP_001859.1	P15085

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA1	ENST00000011292.8	TSL:1 MANE Select	c.9delG	p.Leu4CysfsTer4	frameshift	Exon 1 of 10	ENSP00000011292.3	P15085
	CPA1	ENST00000604896.5	TSL:3	c.9delG	p.Leu4CysfsTer4	frameshift	Exon 1 of 6	ENSP00000475021.2	S4R433
	CPA1	ENST00000481342.5	TSL:3	c.-200+120delG		intron	N/A	ENSP00000420218.1	C9JQ63

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.60e-7 AC: 1 AN: 1162502 Hom.: 0 Cov.: 29 AF XY: 0.00000180 AC XY: 1 AN XY: 556956

African (AFR) AF: 0.00 AC: 0 AN: 24952

American (AMR) AF: 0.00 AC: 0 AN: 17830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15394

East Asian (EAS) AF: 0.00 AC: 0 AN: 30536

South Asian (SAS) AF: 0.00 AC: 0 AN: 26902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4630

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 955488

Other (OTH) AF: 0.00 AC: 0 AN: 46514

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1796390308; hg19: chr7-130020365;