rs10517844

Positions:

• chr4-165413239-T-C

Variant summary

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

The ENST00000402744.9(CPE):​c.307+33711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,090 control chromosomes in the GnomAD database, including 6,422 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 0.29 (6422 hom., cov: 32)
• Consequence: CPE ENST00000402744.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

Genes affected

CPE (HGNC:2303): (carboxypeptidase E) This gene encodes a member of the M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature peptidase. This peripheral membrane protein cleaves C-terminal amino acid residues and is involved in the biosynthesis of peptide hormones and neurotransmitters, including insulin. This protein may also function independently of its peptidase activity, as a neurotrophic factor that promotes neuronal survival, and as a sorting receptor that binds to regulated secretory pathway proteins, including prohormones. Mutations in this gene are implicated in type 2 diabetes. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPE	NM_001873.4	c.307+33711T>C		intron_variant		ENST00000402744.9	NP_001864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPE	ENST00000402744.9	c.307+33711T>C		intron_variant		1	NM_001873.4	ENSP00000386104	P1
CPE	ENST00000513982.5	c.-29-51151T>C		intron_variant		4		ENSP00000424830

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43608 AN: 151972 Hom.: 6412 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.287 AC: 43649 AN: 152090 Hom.: 6422 Cov.: 32 AF XY: 0.284 AC XY: 21120 AN XY: 74316

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.307

Alfa AF: 0.309 Hom.: 3801

Bravo AF: 0.283

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10517844; hg19: chr4-166334391;