rs6536911

Variant names:

• chr4-165371675-C-T
• rs6536911
• ENST00000513982.5:c.-30+10364C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513982.5(CPE):​c.-30+10364C>T 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 151,730 control chromosomes in the GnomAD database, including 2,298 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 (2298 hom., cov: 32)
• Consequence: CPE ENST00000513982.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPE	ENST00000513982.5	c.-30+10364C>T		intron_variant	Intron 1 of 3	4		ENSP00000424830.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23947 AN: 151612 Hom.: 2291 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.158 AC: 23972 AN: 151730 Hom.: 2298 Cov.: 32 AF XY: 0.154 AC XY: 11439 AN XY: 74136

African (AFR) AF: 0.267 AC: 11047 AN: 41394

American (AMR) AF: 0.125 AC: 1901 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3470

East Asian (EAS) AF: 0.150 AC: 774 AN: 5168

South Asian (SAS) AF: 0.160 AC: 768 AN: 4808

European-Finnish (FIN) AF: 0.112 AC: 1168 AN: 10464

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

European-Non Finnish (NFE) AF: 0.111 AC: 7547 AN: 67854

Other (OTH) AF: 0.151 AC: 318 AN: 2108

Alfa AF: 0.139 Hom.: 208

Bravo AF: 0.162

Asia WGS AF: 0.164 AC: 569 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.25
PhyloP100		-0.50

Splicing

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

Other links and lift over

dbSNP: rs6536911; hg19: chr4-166292827;