7-130383698-C-T

Variant names:

• chr7-130383698-C-T
• rs12706927
• NM_001868.4:c.600C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001868.4(CPA1):​c.600C>T​(p.Tyr200Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,612,562 control chromosomes in the GnomAD database, including 10,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (876 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9291 hom.)
• Consequence: CPA1 NM_001868.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.198
• Publications: 9 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 7-130383698-C-T is Benign according to our data. Variant chr7-130383698-C-T is described in ClinVar as Benign. ClinVar VariationId is 258476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.198 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

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.600C>T	p.Tyr200Tyr	synonymous	Exon 6 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.600C>T	p.Tyr200Tyr	synonymous	Exon 6 of 10	ENSP00000011292.3	P15085
	CPA1	ENST00000484324.1	TSL:5	c.336C>T	p.Tyr112Tyr	synonymous	Exon 5 of 9	ENSP00000419497.1	C9JUF9
	CPA1	ENST00000476062.5	TSL:5	c.336C>T	p.Tyr112Tyr	synonymous	Exon 6 of 9	ENSP00000419408.1	C9JUZ4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15766 AN: 152136 Hom.: 877 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.0991 AC: 24906 AN: 251294 AF XY: 0.103

Gnomad AFR exome AF: 0.0955

Gnomad AMR exome AF: 0.0541

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.00179

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.109 AC: 159427 AN: 1460308 Hom.: 9291 Cov.: 31 AF XY: 0.109 AC XY: 79537 AN XY: 726566

African (AFR) AF: 0.0891 AC: 2980 AN: 33456

American (AMR) AF: 0.0556 AC: 2485 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2742 AN: 26126

East Asian (EAS) AF: 0.00118 AC: 47 AN: 39700

South Asian (SAS) AF: 0.103 AC: 8843 AN: 86206

European-Finnish (FIN) AF: 0.115 AC: 6153 AN: 53400

Middle Eastern (MID) AF: 0.155 AC: 892 AN: 5760

European-Non Finnish (NFE) AF: 0.116 AC: 129096 AN: 1110602

Other (OTH) AF: 0.103 AC: 6189 AN: 60338

GnomAD4 genome AF: 0.104 AC: 15764 AN: 152254 Hom.: 876 Cov.: 32 AF XY: 0.102 AC XY: 7619 AN XY: 74426

African (AFR) AF: 0.0938 AC: 3899 AN: 41550

American (AMR) AF: 0.0830 AC: 1270 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5176

South Asian (SAS) AF: 0.104 AC: 503 AN: 4826

European-Finnish (FIN) AF: 0.125 AC: 1324 AN: 10610

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8102 AN: 68004

Other (OTH) AF: 0.114 AC: 240 AN: 2108

Alfa AF: 0.109 Hom.: 1714

Bravo AF: 0.0990

Asia WGS AF: 0.0530 AC: 186 AN: 3478

EpiCase AF: 0.125

EpiControl AF: 0.121

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hereditary pancreatitis (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.3
DANN	Benign	0.27
PhyloP100		-0.20
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12706927; hg19: chr7-130023539;