4-165438269-T-G

Variant names:

• chr4-165438269-T-G
• rs4481204
• NM_001873.4:c.308-26121T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001873.4(CPE):​c.308-26121T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: CPE NM_001873.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPE	NM_001873.4	MANE Select	c.308-26121T>G		intron	N/A	NP_001864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPE	ENST00000402744.9	TSL:1 MANE Select	c.308-26121T>G		intron	N/A	ENSP00000386104.4
	CPE	ENST00000511992.1	TSL:5	c.-30+19981T>G		intron	N/A	ENSP00000423699.1
	CPE	ENST00000431967.5	TSL:4	c.-30+23023T>G		intron	N/A	ENSP00000416601.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.023
DANN	Benign	0.43
PhyloP100		-1.0

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: rs4481204; hg19: chr4-166359421;