5-65051794-A-G

Variant names:

• chr5-65051794-A-G
• rs266590
• ENST00000693303.1:c.1153-47458A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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)

ENSG00000300387 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWC27	ENST00000693303.1	c.1153-47458A>G		intron_variant	Intron 12 of 12			ENSP00000508557.1
ENSG00000300387	ENST00000771265.1	n.70+383A>G		intron_variant	Intron 1 of 2
ENSG00000300387	ENST00000771266.1	n.103+383A>G		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.507 AC: 21017 AN: 41426

American (AMR) AF: 0.545 AC: 8329 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5162

South Asian (SAS) AF: 0.513 AC: 2472 AN: 4822

European-Finnish (FIN) AF: 0.656 AC: 6891 AN: 10502

Middle Eastern (MID) AF: 0.645 AC: 187 AN: 290

European-Non Finnish (NFE) AF: 0.663 AC: 45067 AN: 67952

Other (OTH) AF: 0.615 AC: 1296 AN: 2108

Alfa AF: 0.634 Hom.: 72349

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
PhyloP100		2.7

Splicing

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

Other links and lift over

dbSNP: rs266590; hg19: chr5-64347621;