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GeneBe

10-100065200-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001308.3(CPN1):c.747G>A(p.Lys249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,613,268 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 20 hom. )

Consequence

CPN1
NM_001308.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07
Variant links:
Genes affected
CPN1 (HGNC:2312): (carboxypeptidase N subunit 1) Carboxypeptidase N is a plasma metallo-protease that cleaves basic amino acids from the C terminal of peptides and proteins. The enzyme is important in the regulation of peptides like kinins and anaphylatoxins, and has also been known as kininase-1 and anaphylatoxin inactivator. This enzyme is a tetramer comprised of two identical regulatory subunits and two identical catalytic subunits; this gene encodes the catalytic subunit. Mutations in this gene can be associated with angioedema or chronic urticaria resulting from carboxypeptidase N deficiency. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-100065200-C-T is Benign according to our data. Variant chr10-100065200-C-T is described in ClinVar as [Benign]. Clinvar id is 780887.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.07 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1669/152310) while in subpopulation AFR AF= 0.0384 (1598/41578). AF 95% confidence interval is 0.0369. There are 26 homozygotes in gnomad4. There are 771 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPN1NM_001308.3 linkuse as main transcriptc.747G>A p.Lys249= synonymous_variant 4/9 ENST00000370418.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPN1ENST00000370418.8 linkuse as main transcriptc.747G>A p.Lys249= synonymous_variant 4/91 NM_001308.3 P1
CPN1ENST00000441382.1 linkuse as main transcriptc.138G>A p.Lys46= synonymous_variant 1/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0109
AC:
1666
AN:
152192
Hom.:
26
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0385
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00367
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00528
GnomAD3 exomes
AF:
0.00295
AC:
738
AN:
250070
Hom.:
15
AF XY:
0.00219
AC XY:
296
AN XY:
135302
show subpopulations
Gnomad AFR exome
AF:
0.0382
Gnomad AMR exome
AF:
0.00281
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000133
Gnomad OTH exome
AF:
0.00213
GnomAD4 exome
AF:
0.00100
AC:
1463
AN:
1460958
Hom.:
20
Cov.:
31
AF XY:
0.000812
AC XY:
590
AN XY:
726620
show subpopulations
Gnomad4 AFR exome
AF:
0.0343
Gnomad4 AMR exome
AF:
0.00298
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00243
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1669
AN:
152310
Hom.:
26
Cov.:
32
AF XY:
0.0104
AC XY:
771
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0384
Gnomad4 AMR
AF:
0.00366
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00522
Alfa
AF:
0.00529
Hom.:
8
Bravo
AF:
0.0120
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
7.6
Dann
Benign
0.40

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs74152964; hg19: chr10-101824957; API