rs266590

Positions:

• chr5-65051794-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000693303.1(CWC27):​c.1153-47458A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,918 control chromosomes in the GnomAD database, including 27,226 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 0.59 (27226 hom., cov: 31)
• Consequence: CWC27 ENST00000693303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWC27	ENST00000693303.1	c.1153-47458A>G		intron_variant				ENSP00000508557

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89589 AN: 151798 Hom.: 27226 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.590 AC: 89624 AN: 151918 Hom.: 27226 Cov.: 31 AF XY: 0.585 AC XY: 43424 AN XY: 74228

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.615

Alfa AF: 0.651 Hom.: 39938

Bravo AF: 0.574

Asia WGS AF: 0.405 AC: 1414 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs266590; hg19: chr5-64347621;