rs1059502

Variant names:

• chr3-148844523-G-A
• rs1059502
• NM_001871.3:c.622G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001871.3(CPB1):​c.622G>A​(p.Asp208Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,612,786 control chromosomes in the GnomAD database, including 44,685 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D208A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.24 (4630 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40055 hom.)
• Consequence: CPB1 NM_001871.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.624
• Publications: 28 publications found

Genes affected

CPB1 (HGNC:2299): (carboxypeptidase B1) Three different procarboxypeptidases A and two different procarboxypeptidases B have been isolated. The B1 and B2 forms differ from each other mainly in isoelectric point. Carboxypeptidase B1 is a highly tissue-specific protein and is a useful serum marker for acute pancreatitis and dysfunction of pancreatic transplants. It is not elevated in pancreatic carcinoma. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.2314997E-4).
• BP6: Variant 3-148844523-G-A is Benign according to our data. Variant chr3-148844523-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059113.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001871.3. 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
	CPB1	NM_001871.3	MANE Select	c.622G>A	p.Asp208Asn	missense	Exon 7 of 11	NP_001862.2	P15086

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB1	ENST00000282957.9	TSL:1 MANE Select	c.622G>A	p.Asp208Asn	missense	Exon 7 of 11	ENSP00000282957.4	P15086
	CPB1	ENST00000491148.5	TSL:5	c.622G>A	p.Asp208Asn	missense	Exon 8 of 12	ENSP00000417222.1	P15086
	CPB1	ENST00000968620.1		c.295G>A	p.Asp99Asn	missense	Exon 4 of 8	ENSP00000638679.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37011 AN: 151944 Hom.: 4624 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.224 AC: 56168 AN: 250960 AF XY: 0.226

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.231 AC: 337317 AN: 1460724 Hom.: 40055 Cov.: 34 AF XY: 0.232 AC XY: 168553 AN XY: 726678

African (AFR) AF: 0.311 AC: 10411 AN: 33442

American (AMR) AF: 0.152 AC: 6780 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3317 AN: 26114

East Asian (EAS) AF: 0.240 AC: 9514 AN: 39686

South Asian (SAS) AF: 0.282 AC: 24319 AN: 86208

European-Finnish (FIN) AF: 0.230 AC: 12281 AN: 53398

Middle Eastern (MID) AF: 0.109 AC: 630 AN: 5766

European-Non Finnish (NFE) AF: 0.231 AC: 256821 AN: 1111056

Other (OTH) AF: 0.219 AC: 13244 AN: 60354

GnomAD4 genome AF: 0.244 AC: 37036 AN: 152062 Hom.: 4630 Cov.: 32 AF XY: 0.242 AC XY: 17955 AN XY: 74342

African (AFR) AF: 0.308 AC: 12789 AN: 41482

American (AMR) AF: 0.176 AC: 2689 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1316 AN: 5166

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4818

European-Finnish (FIN) AF: 0.237 AC: 2504 AN: 10578

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15168 AN: 67984

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.223 Hom.: 13204

Bravo AF: 0.239

TwinsUK AF: 0.239 AC: 888

ALSPAC AF: 0.226 AC: 871

ESP6500AA AF: 0.308 AC: 1358

ESP6500EA AF: 0.206 AC: 1769

ExAC AF: 0.229 AC: 27749

Asia WGS AF: 0.292 AC: 1016 AN: 3478

EpiCase AF: 0.208

EpiControl AF: 0.205

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CPB1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.24
DANN	Benign	0.27
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.00052	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.67	N
PhyloP100		-0.62
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.013
Sift	Benign	0.88	T
Sift4G	Benign	0.78	T
Polyphen		0.0050	B
Vest4		0.045
MPC		0.20
ClinPred		0.00085	T
GERP RS		-2.8
Varity_R		0.047
gMVP		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1059502; hg19: chr3-148562310; COSMIC: COSV51571859; COSMIC: COSV51571859;