NM_005869.4:c.49T>C

Variant names:

• chr5-64774697-T-C
• rs369814947
• NM_005869.4:c.49T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_005869.4(CWC27):​c.49T>C​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,559,690 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000035 (1 hom.)
• Consequence: CWC27 NM_005869.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.338
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-64774697-T-C is Benign according to our data. Variant chr5-64774697-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 749565.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.338 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000118 (18/152368) while in subpopulation EAS AF = 0.00077 (4/5194). AF 95% confidence interval is 0.000263. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWC27	NM_005869.4	MANE Select	c.49T>C	p.Leu17Leu	synonymous	Exon 2 of 14	NP_005860.2	Q6UX04-1
	CWC27	NM_001297644.1		c.49T>C	p.Leu17Leu	synonymous	Exon 2 of 13	NP_001284573.1	Q6UX04
	CWC27	NM_001297645.2		c.49T>C	p.Leu17Leu	synonymous	Exon 2 of 11	NP_001284574.1	D6REK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWC27	ENST00000381070.8	TSL:1 MANE Select	c.49T>C	p.Leu17Leu	synonymous	Exon 2 of 14	ENSP00000370460.2	Q6UX04-1
	CWC27	ENST00000508024.2	TSL:1	c.49T>C	p.Leu17Leu	synonymous	Exon 2 of 11	ENSP00000426802.1	D6REK3
	CWC27	ENST00000607786.2	TSL:6	c.-252T>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	ENSP00000509647.1	A0A8I5KY88

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000859 AC: 18 AN: 209620 AF XY: 0.000105

Gnomad AFR exome AF: 0.000282

Gnomad AMR exome AF: 0.0000428

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000636

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000348 AC: 49 AN: 1407322 Hom.: 1 Cov.: 26 AF XY: 0.0000314 AC XY: 22 AN XY: 700188

African (AFR) AF: 0.0000652 AC: 2 AN: 30692

American (AMR) AF: 0.0000286 AC: 1 AN: 34972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24420

East Asian (EAS) AF: 0.000369 AC: 14 AN: 37964

South Asian (SAS) AF: 0.000143 AC: 11 AN: 77116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5126

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1087564

Other (OTH) AF: 0.000345 AC: 20 AN: 57940

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152368 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74518

African (AFR) AF: 0.000289 AC: 12 AN: 41590

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

Asia WGS AF: 0.00434 AC: 15 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CWC27-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.9
DANN	Benign	0.73
PhyloP100		0.34

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: rs369814947; hg19: chr5-64070524;