chr4-165469203-C-T

Position:

• chr4-165469203-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPE	NM_001873.4	c.672+1348C>T		intron_variant		ENST00000402744.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPE	ENST00000402744.9	c.672+1348C>T		intron_variant		1	NM_001873.4	P1
CPE	ENST00000431967.5	c.336+1348C>T		intron_variant		4
CPE	ENST00000511992.1	c.336+1348C>T		intron_variant		5
CPE	ENST00000513982.5	c.336+1348C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.713

Alfa AF: 0.702 Hom.: 34949

Bravo AF: 0.725

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs1370687; hg19: chr4-166390355;