rs11724658

Positions:

• chr4-165372928-G-A

Variant summary

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

The ENST00000513982.5(CPE):​c.-30+11617G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,894 control chromosomes in the GnomAD database, including 2,316 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 0.16 (2316 hom., cov: 33)
• Consequence: CPE ENST00000513982.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.165372928G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPE	ENST00000513982.5	c.-30+11617G>A		intron_variant		4		ENSP00000424830.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24042 AN: 151776 Hom.: 2308 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.158 AC: 24073 AN: 151894 Hom.: 2316 Cov.: 33 AF XY: 0.155 AC XY: 11496 AN XY: 74230

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.156

Alfa AF: 0.136 Hom.: 276

Bravo AF: 0.163

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.83
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11724658; hg19: chr4-166294080;