rs6875372

Variant names:

• chr5-64783188-T-A
• rs6875372
• NM_005869.4:c.253-648T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005869.4(CWC27):​c.253-648T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,980 control chromosomes in the GnomAD database, including 22,669 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 0.54 (22669 hom., cov: 32)
• Consequence: CWC27 NM_005869.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005869.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWC27	NM_005869.4	MANE Select	c.253-648T>A		intron	N/A	NP_005860.2
	CWC27	NM_001297644.1		c.253-648T>A		intron	N/A	NP_001284573.1
	CWC27	NM_001297645.2		c.253-648T>A		intron	N/A	NP_001284574.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWC27	ENST00000381070.8	TSL:1 MANE Select	c.253-648T>A		intron	N/A	ENSP00000370460.2
	CWC27	ENST00000508024.2	TSL:1	c.253-648T>A		intron	N/A	ENSP00000426802.1
	CWC27	ENST00000693660.1		c.253-648T>A		intron	N/A	ENSP00000509052.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81943 AN: 151862 Hom.: 22648 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.540 AC: 82008 AN: 151980 Hom.: 22669 Cov.: 32 AF XY: 0.548 AC XY: 40665 AN XY: 74256

African (AFR) AF: 0.526 AC: 21783 AN: 41450

American (AMR) AF: 0.486 AC: 7425 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4373 AN: 5170

South Asian (SAS) AF: 0.737 AC: 3562 AN: 4830

European-Finnish (FIN) AF: 0.620 AC: 6538 AN: 10538

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35215 AN: 67942

Other (OTH) AF: 0.507 AC: 1069 AN: 2108

Alfa AF: 0.541 Hom.: 2782

Bravo AF: 0.525

Asia WGS AF: 0.777 AC: 2693 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.30
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6875372; hg19: chr5-64079015;