rs2191351

chr17-30432017-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304.5(CPD):c.2127+136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 622,256 control chromosomes in the GnomAD database, including 105,143 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (30732 hom., cov: 32)
  • Exomes 𝑓: 0.55 (74411 hom.)
• Consequence: CPD NM_001304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

CPD (HGNC:2301): (carboxypeptidase D) The metallocarboxypeptidase family of enzymes is divided into 2 subfamilies based on sequence similarities. The pancreatic carboxypeptidase-like and the regulatory B-type carboxypeptidase subfamilies. Carboxypeptidase D has been identified as a regulatory B-type carboxypeptidase. CPD is a homolog of duck gp180, a hepatitis B virus-binding protein. Transcript variants utilizing alternative polyadenylation signals exist for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPD	NM_001304.5	c.2127+136T>C		intron_variant		ENST00000225719.9
CPD	NM_001199775.1	c.1386+136T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPD	ENST00000225719.9	c.2127+136T>C		intron_variant		1	NM_001304.5	P1
CPD	ENST00000543464.6	c.1386+136T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94284 AN: 152016 Hom.: 30691 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.555 AC: 260799 AN: 470122 Hom.: 74411 AF XY: 0.552 AC XY: 137983 AN XY: 250136

Gnomad4 AFR exome AF: 0.822

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.620 AC: 94375 AN: 152134 Hom.: 30732 Cov.: 32 AF XY: 0.622 AC XY: 46279 AN XY: 74366

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.602

Alfa AF: 0.545 Hom.: 10519

Bravo AF: 0.634

Asia WGS AF: 0.665 AC: 2313 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.73
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2191351; hg19: chr17-28759035;