17-30393723-A-C

Position:

• chr17-30393723-A-C

Variant summary

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

The NM_001304.5(CPD):​c.994+8487A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,052 control chromosomes in the GnomAD database, including 15,754 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 0.44 (15754 hom., cov: 32)
• Consequence: CPD NM_001304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPD	NM_001304.5	c.994+8487A>C		intron_variant		ENST00000225719.9	NP_001295.2
CPD	NM_001199775.1	c.253+8487A>C		intron_variant			NP_001186704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPD	ENST00000225719.9	c.994+8487A>C		intron_variant		1	NM_001304.5	ENSP00000225719	P1
CPD	ENST00000543464.6	c.253+8487A>C		intron_variant		2		ENSP00000444443

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67511 AN: 151934 Hom.: 15749 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.444 AC: 67533 AN: 152052 Hom.: 15754 Cov.: 32 AF XY: 0.449 AC XY: 33346 AN XY: 74294

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.465

Alfa AF: 0.463 Hom.: 33116

Bravo AF: 0.448

Asia WGS AF: 0.622 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.53

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: rs3794794; hg19: chr17-28720741;