Menu
GeneBe

5-64774697-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_005869.4(CWC27):c.49T>C(p.Leu17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,559,690 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000035 ( 1 hom. )

Consequence

CWC27
NM_005869.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.338
Variant links:
Genes affected
CWC27 (HGNC:10664): (CWC27 spliceosome associated cyclophilin) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein peptidyl-prolyl isomerization. Located in nucleoplasm. Part of U2-type precatalytic spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-64774697-T-C is Benign according to our data. Variant chr5-64774697-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 749565.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=0.338 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000118 (18/152368) while in subpopulation EAS AF= 0.00077 (4/5194). AF 95% confidence interval is 0.000263. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CWC27NM_005869.4 linkuse as main transcriptc.49T>C p.Leu17= synonymous_variant 2/14 ENST00000381070.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CWC27ENST00000381070.8 linkuse as main transcriptc.49T>C p.Leu17= synonymous_variant 2/141 NM_005869.4 P1Q6UX04-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000118
AC:
18
AN:
152250
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000768
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000859
AC:
18
AN:
209620
Hom.:
0
AF XY:
0.000105
AC XY:
12
AN XY:
114338
show subpopulations
Gnomad AFR exome
AF:
0.000282
Gnomad AMR exome
AF:
0.0000428
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000636
Gnomad SAS exome
AF:
0.000175
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000348
AC:
49
AN:
1407322
Hom.:
1
Cov.:
26
AF XY:
0.0000314
AC XY:
22
AN XY:
700188
show subpopulations
Gnomad4 AFR exome
AF:
0.0000652
Gnomad4 AMR exome
AF:
0.0000286
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000369
Gnomad4 SAS exome
AF:
0.000143
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.19e-7
Gnomad4 OTH exome
AF:
0.000345
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000118
AC:
18
AN:
152368
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000770
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.0000793
Asia WGS
AF:
0.00434
AC:
15
AN:
3474

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 26, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
6.9
Dann
Benign
0.73

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: rs369814947; hg19: chr5-64070524; API