5-64813287-T-C

Position:

• chr5-64813287-T-C

Variant summary

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

The NM_005869.4(CWC27):​c.938+8901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,996 control chromosomes in the GnomAD database, including 11,329 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 0.37 (11329 hom., cov: 32)
• Consequence: CWC27 NM_005869.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CWC27	NM_005869.4	c.938+8901T>C		intron_variant		ENST00000381070.8
CWC27	NM_001297644.1	c.938+8901T>C		intron_variant
CWC27	NM_001318000.2	c.938+8901T>C		intron_variant
CWC27	NM_001364478.1	c.938+8901T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWC27	ENST00000381070.8	c.938+8901T>C		intron_variant		1	NM_005869.4	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56554 AN: 151878 Hom.: 11303 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.373 AC: 56624 AN: 151996 Hom.: 11329 Cov.: 32 AF XY: 0.371 AC XY: 27587 AN XY: 74322

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.331

Alfa AF: 0.324 Hom.: 1385

Bravo AF: 0.366

Asia WGS AF: 0.488 AC: 1693 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs1433612; hg19: chr5-64109114;