5-64769116-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005869.4(CWC27):c.-31G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,607,344 control chromosomes in the GnomAD database, including 57,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (14616 hom., cov: 32)
  • Exomes 𝑓: 0.21 (42449 hom.)
• Consequence: CWC27 NM_005869.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.62

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-64769116-G-A is Benign according to our data. Variant chr5-64769116-G-A is described in ClinVar as [Benign]. Clinvar id is 1255435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CWC27	NM_005869.4	c.-31G>A		5_prime_UTR_variant	1/14	ENST00000381070.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWC27	ENST00000381070.8	c.-31G>A		5_prime_UTR_variant	1/14	1	NM_005869.4	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53494 AN: 151882 Hom.: 14573 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.254 AC: 63831 AN: 251030 Hom.: 12074 AF XY: 0.250 AC XY: 33896 AN XY: 135692

Gnomad AFR exome AF: 0.768

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.549

Gnomad SAS exome AF: 0.333

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.212 AC: 309071 AN: 1455344 Hom.: 42449 Cov.: 29 AF XY: 0.213 AC XY: 154569 AN XY: 724404

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.525

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.353 AC: 53593 AN: 152000 Hom.: 14616 Cov.: 32 AF XY: 0.347 AC XY: 25784 AN XY: 74304

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.316

Alfa AF: 0.207 Hom.: 8725

Bravo AF: 0.374

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.16
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1363953; hg19: chr5-64064943; COSMIC: COSV66884545; COSMIC: COSV66884545;