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GeneBe

6-36774990-C-T

Variant summary

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

The NM_020939.2(CPNE5):c.708G>A(p.Val236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,166 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 15 hom., cov: 33)
Exomes 𝑓: 0.00075 ( 5 hom. )

Consequence

CPNE5
NM_020939.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.778
Variant links:
Genes affected
CPNE5 (HGNC:2318): (copine 5) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

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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=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-36774990-C-T is Benign according to our data. Variant chr6-36774990-C-T is described in ClinVar as [Benign]. Clinvar id is 773197.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=0.778 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 = 0.00855 (1302/152322) while in subpopulation AFR AF= 0.0294 (1220/41556). AF 95% confidence interval is 0.028. There are 15 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPNE5NM_020939.2 linkuse as main transcriptc.708G>A p.Val236= synonymous_variant 10/21 ENST00000244751.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPNE5ENST00000244751.7 linkuse as main transcriptc.708G>A p.Val236= synonymous_variant 10/211 NM_020939.2 A1Q9HCH3-1
CPNE5ENST00000633136.2 linkuse as main transcriptc.759G>A p.Val253= synonymous_variant 11/225 P3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00844
AC:
1284
AN:
152204
Hom.:
13
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0290
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00432
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00621
GnomAD3 exomes
AF:
0.00204
AC:
514
AN:
251432
Hom.:
7
AF XY:
0.00146
AC XY:
199
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.0277
Gnomad AMR exome
AF:
0.00171
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:
0.00000879
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000755
AC:
1103
AN:
1461844
Hom.:
5
Cov.:
30
AF XY:
0.000671
AC XY:
488
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0269
Gnomad4 AMR exome
AF:
0.00197
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00146
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00855
AC:
1302
AN:
152322
Hom.:
15
Cov.:
33
AF XY:
0.00834
AC XY:
621
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0294
Gnomad4 AMR
AF:
0.00431
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00615
Alfa
AF:
0.00440
Hom.:
4
Bravo
AF:
0.00985
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

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 testingInvitaeApr 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
12
Dann
Benign
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs35931885; hg19: chr6-36742767; API