chr5-64884059-A-G

Position:

• chr5-64884059-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWC27	NM_005869.4	c.939-1384A>G		intron_variant		ENST00000381070.8	NP_005860.2
CWC27	NM_001297644.1	c.939-1384A>G		intron_variant			NP_001284573.1
CWC27	NM_001364478.1	c.939-1384A>G		intron_variant			NP_001351407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWC27	ENST00000381070.8	c.939-1384A>G		intron_variant		1	NM_005869.4	ENSP00000370460	P1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59435 AN: 151692 Hom.: 12607 Cov.: 30

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: 2 AN: 8 Hom.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.392 AC: 59527 AN: 151810 Hom.: 12650 Cov.: 30 AF XY: 0.390 AC XY: 28960 AN XY: 74170

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.363

Alfa AF: 0.335 Hom.: 14976

Bravo AF: 0.389

Asia WGS AF: 0.506 AC: 1757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.3
DANN	Benign	0.89

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: rs6897941; hg19: chr5-64179886;