17-30433921-C-G

Variant names:

• chr17-30433921-C-G
• rs9913237
• NM_001304.5:c.2127+2040C>G

Variant summary

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

The NM_001304.5(CPD):​c.2127+2040C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,014 control chromosomes in the GnomAD database, including 21,206 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 (21206 hom., cov: 32)
• Consequence: CPD NM_001304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPD	NM_001304.5	MANE Select	c.2127+2040C>G		intron	N/A	NP_001295.2
	CPD	NM_001199775.1		c.1386+2040C>G		intron	N/A	NP_001186704.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPD	ENST00000225719.9	TSL:1 MANE Select	c.2127+2040C>G		intron	N/A	ENSP00000225719.4
	CPD	ENST00000543464.6	TSL:2	c.1386+2040C>G		intron	N/A	ENSP00000444443.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78903 AN: 151898 Hom.: 21189 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.519 AC: 78963 AN: 152014 Hom.: 21206 Cov.: 32 AF XY: 0.522 AC XY: 38825 AN XY: 74320

African (AFR) AF: 0.610 AC: 25286 AN: 41448

American (AMR) AF: 0.527 AC: 8052 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3470

East Asian (EAS) AF: 0.832 AC: 4304 AN: 5170

South Asian (SAS) AF: 0.517 AC: 2492 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4447 AN: 10560

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

European-Non Finnish (NFE) AF: 0.456 AC: 31017 AN: 67964

Other (OTH) AF: 0.525 AC: 1109 AN: 2112

Alfa AF: 0.320 Hom.: 736

Bravo AF: 0.534

Asia WGS AF: 0.644 AC: 2239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.68
DANN	Benign	0.35
PhyloP100		-0.50
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: rs9913237; hg19: chr17-28760939;