rs12651884

Variant names:

• chr5-64839186-A-G
• rs12651884
• NM_005869.4:c.938+34800A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-64839186-A-G
• chr5-64839186-A-T

Variant summary

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

The NM_005869.4(CWC27):​c.938+34800A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,992 control chromosomes in the GnomAD database, including 8,882 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 0.34 (8882 hom., cov: 32)
• Consequence: CWC27 NM_005869.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 0 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)

ENSG00000304095 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWC27	NM_005869.4	c.938+34800A>G		intron_variant	Intron 10 of 13	ENST00000381070.8	NP_005860.2
CWC27	NM_001297644.1	c.938+34800A>G		intron_variant	Intron 10 of 12		NP_001284573.1
CWC27	NM_001364478.1	c.938+34800A>G		intron_variant	Intron 10 of 11		NP_001351407.1
CWC27	NM_001318000.2	c.939-5737A>G		intron_variant	Intron 10 of 10		NP_001304929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWC27	ENST00000381070.8	c.938+34800A>G		intron_variant	Intron 10 of 13	1	NM_005869.4	ENSP00000370460.2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50932 AN: 151874 Hom.: 8869 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.335 AC: 50971 AN: 151992 Hom.: 8882 Cov.: 32 AF XY: 0.336 AC XY: 24958 AN XY: 74286

African (AFR) AF: 0.371 AC: 15374 AN: 41450

American (AMR) AF: 0.206 AC: 3141 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2624 AN: 5166

South Asian (SAS) AF: 0.406 AC: 1951 AN: 4808

European-Finnish (FIN) AF: 0.352 AC: 3718 AN: 10550

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22377 AN: 67952

Other (OTH) AF: 0.308 AC: 650 AN: 2110

Alfa AF: 0.328 Hom.: 1034

Bravo AF: 0.325

Asia WGS AF: 0.477 AC: 1653 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.70
PhyloP100		-0.069
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: rs12651884; hg19: chr5-64135013;