rs6536911

Positions:

• chr4-165371675-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPE	ENST00000513982.5	c.-30+10364C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.151

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6536911; hg19: chr4-166292827;