rs1370687

Variant names:

• chr4-165469203-C-T
• rs1370687
• NM_001873.4:c.672+1348C>T

Variant summary

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

The NM_001873.4(CPE):​c.672+1348C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,086 control chromosomes in the GnomAD database, including 40,869 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 0.73 (40869 hom., cov: 32)
• Consequence: CPE NM_001873.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001873.4. 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
	CPE	NM_001873.4	MANE Select	c.672+1348C>T		intron	N/A	NP_001864.1	P16870-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPE	ENST00000402744.9	TSL:1 MANE Select	c.672+1348C>T		intron	N/A	ENSP00000386104.4	P16870-1
	CPE	ENST00000957033.1		c.672+1348C>T		intron	N/A	ENSP00000627092.1
	CPE	ENST00000871530.1		c.672+1348C>T		intron	N/A	ENSP00000541589.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111042 AN: 151968 Hom.: 40834 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.731 AC: 111136 AN: 152086 Hom.: 40869 Cov.: 32 AF XY: 0.731 AC XY: 54325 AN XY: 74348

African (AFR) AF: 0.798 AC: 33082 AN: 41472

American (AMR) AF: 0.644 AC: 9837 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2302 AN: 3470

East Asian (EAS) AF: 0.783 AC: 4046 AN: 5170

South Asian (SAS) AF: 0.619 AC: 2984 AN: 4820

European-Finnish (FIN) AF: 0.810 AC: 8576 AN: 10590

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47872 AN: 67982

Other (OTH) AF: 0.713 AC: 1504 AN: 2110

Alfa AF: 0.705 Hom.: 53316

Bravo AF: 0.725

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.31
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1370687; hg19: chr4-166390355;