rs719601

Variant names:

• chr17-30404397-G-A
• rs719601
• NM_001304.5:c.995-16444G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304.5(CPD):​c.995-16444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,922 control chromosomes in the GnomAD database, including 20,827 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 0.52 (20827 hom., cov: 32)
• Consequence: CPD NM_001304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPD	NM_001304.5	c.995-16444G>A		intron_variant	Intron 2 of 20	ENST00000225719.9	NP_001295.2
CPD	NM_001199775.1	c.254-16444G>A		intron_variant	Intron 2 of 20		NP_001186704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPD	ENST00000225719.9	c.995-16444G>A		intron_variant	Intron 2 of 20	1	NM_001304.5	ENSP00000225719.4
CPD	ENST00000543464.6	c.254-16444G>A		intron_variant	Intron 2 of 20	2		ENSP00000444443.2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78301 AN: 151804 Hom.: 20814 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.516 AC: 78353 AN: 151922 Hom.: 20827 Cov.: 32 AF XY: 0.519 AC XY: 38507 AN XY: 74262

African (AFR) AF: 0.599 AC: 24816 AN: 41440

American (AMR) AF: 0.526 AC: 8035 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3468

East Asian (EAS) AF: 0.822 AC: 4263 AN: 5186

South Asian (SAS) AF: 0.515 AC: 2485 AN: 4822

European-Finnish (FIN) AF: 0.421 AC: 4433 AN: 10526

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30967 AN: 67880

Other (OTH) AF: 0.520 AC: 1096 AN: 2108

Alfa AF: 0.496 Hom.: 3996

Bravo AF: 0.529

Asia WGS AF: 0.636 AC: 2206 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.62
PhyloP100		-2.7
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: rs719601; hg19: chr17-28731415;