rs1248250862

Variant names:

• chr17-30379213-G-A
• rs1248250862
• NM_001304.5:c.233G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-30379213-G-A
• chr17-30379213-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001304.5(CPD):​c.233G>A​(p.Gly78Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G78V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPD NM_001304.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30514058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPD	NM_001304.5	c.233G>A	p.Gly78Asp	missense_variant	Exon 1 of 21	ENST00000225719.9	NP_001295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPD	ENST00000225719.9	c.233G>A	p.Gly78Asp	missense_variant	Exon 1 of 21	1	NM_001304.5	ENSP00000225719.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1376052 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 679178

African (AFR) AF: 0.00 AC: 0 AN: 29184

American (AMR) AF: 0.00 AC: 0 AN: 35306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24700

East Asian (EAS) AF: 0.00 AC: 0 AN: 34050

South Asian (SAS) AF: 0.00 AC: 0 AN: 78822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074876

Other (OTH) AF: 0.00 AC: 0 AN: 57488

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0018	T
Eigen	Benign	0.049
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.065	N
PhyloP100		1.6
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	0.37	N
REVEL	Benign	0.11
Sift	Benign	0.79	T
Sift4G	Benign	0.62	T
Polyphen		0.95	P
Vest4		0.30
MutPred		0.44		Loss of loop (P = 0.0512);
MVP		0.36
MPC		2.3
ClinPred		0.60	D
GERP RS		4.2
PromoterAI		-0.26	Neutral
Varity_R		0.15
gMVP		0.90

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: rs1248250862; hg19: chr17-28706231;