chr17-30432017-T-C

Variant names:

• chr17-30432017-T-C
• rs2191351
• NM_001304.5:c.2127+136T>C

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+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
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 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+136T>C		intron	N/A	NP_001295.2
	CPD	NM_001199775.1		c.1386+136T>C		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+136T>C		intron	N/A	ENSP00000225719.4
	CPD	ENST00000543464.6	TSL:2	c.1386+136T>C		intron	N/A	ENSP00000444443.2

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

African (AFR) AF: 0.822 AC: 10360 AN: 12600

American (AMR) AF: 0.573 AC: 9070 AN: 15826

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 7227 AN: 13626

East Asian (EAS) AF: 0.799 AC: 24139 AN: 30214

South Asian (SAS) AF: 0.544 AC: 23361 AN: 42982

European-Finnish (FIN) AF: 0.533 AC: 16232 AN: 30480

Middle Eastern (MID) AF: 0.574 AC: 1144 AN: 1992

European-Non Finnish (NFE) AF: 0.521 AC: 154339 AN: 296060

Other (OTH) AF: 0.567 AC: 14927 AN: 26342

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

African (AFR) AF: 0.817 AC: 33944 AN: 41526

American (AMR) AF: 0.575 AC: 8782 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3468

East Asian (EAS) AF: 0.823 AC: 4268 AN: 5184

South Asian (SAS) AF: 0.545 AC: 2626 AN: 4816

European-Finnish (FIN) AF: 0.534 AC: 5646 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.521 AC: 35386 AN: 67976

Other (OTH) AF: 0.602 AC: 1274 AN: 2116

Alfa AF: 0.546 Hom.: 11886

Bravo AF: 0.634

Asia WGS AF: 0.665 AC: 2313 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.48
PhyloP100		-1.3
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: rs2191351; hg19: chr17-28759035;