rs11724658

Variant names:

• chr4-165372928-G-A
• rs11724658
• ENST00000513982.5:c.-30+11617G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

CPE Gene-Disease associations (from GenCC):

• BDV syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513982.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPE	ENST00000513982.5	TSL:4	c.-30+11617G>A		intron	N/A	ENSP00000424830.1	D6RF88

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

African (AFR) AF: 0.268 AC: 11118 AN: 41430

American (AMR) AF: 0.125 AC: 1915 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3468

East Asian (EAS) AF: 0.150 AC: 778 AN: 5176

South Asian (SAS) AF: 0.160 AC: 766 AN: 4790

European-Finnish (FIN) AF: 0.111 AC: 1171 AN: 10524

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7548 AN: 67910

Other (OTH) AF: 0.156 AC: 328 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.83
DANN	Benign	0.88
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs11724658; hg19: chr4-166294080;