dbSNP rs6897941: CWC27:c.939-1384A>G (chr5-64884059-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005869.4(CWC27):c.939-1384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,818 control chromosomes in the GnomAD database, including 12,650 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 0.39 ( 12650 hom., cov: 30)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

CWC27
NM_005869.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

Publications

1 publications found

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]

CWC27 Gene-Disease associations (from GenCC):

metaphyseal chondrodysplasia-retinitis pigmentosa syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

CWC27 links:

ENSG00000304095 (HGNC:):

ENSG00000304095 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005869.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CWC27	NM_005869.4	MANE Select	c.939-1384A>G	intron	N/A	NP_005860.2
CWC27	NM_001297644.1		c.939-1384A>G	intron	N/A	NP_001284573.1
CWC27	NM_001364478.1		c.939-1384A>G	intron	N/A	NP_001351407.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CWC27	ENST00000381070.8	TSL:1 MANE Select	c.939-1384A>G	intron	N/A	ENSP00000370460.2
CWC27	ENST00000687101.1		n.2671A>G	non_coding_transcript_exon	Exon 1 of 4
CWC27	ENST00000693660.1		c.840-1384A>G	intron	N/A	ENSP00000509052.1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59435

AN:

151692

Hom.:

12607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.392

AC:

59527

AN:

151810

Hom.:

12650

Cov.:

AF XY:

0.390

AC XY:

28960

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.552

AC:

22818

AN:

41368

American (AMR)

AF:

0.234

AC:

3564

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

913

AN:

3468

East Asian (EAS)

AF:

0.522

AC:

2686

AN:

5144

South Asian (SAS)

AF:

0.413

AC:

1983

AN:

4806

European-Finnish (FIN)

AF:

0.355

AC:

3737

AN:

10522

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.335

AC:

22790

AN:

67934

Other (OTH)

AF:

0.363

AC:

765

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1727

3454

5180

6907

8634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.349

Hom.:

27336

Bravo

AF:

0.389

Asia WGS

AF:

0.506

AC:

1757

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.3

(source)

DANN

Benign

0.89

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over