11-94963977-C-T

Position:

• chr11-94963977-C-T

Variant summary

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

The NM_016403.4(CWC15):​c.561-463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 151,862 control chromosomes in the GnomAD database, including 49,114 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 0.80 (49114 hom., cov: 29)
• Consequence: CWC15 NM_016403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

Genes affected

CWC15 (HGNC:26939): (CWC15 spliceosome associated protein homolog) Predicted to enable RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in mitochondrion and nuclear speck. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

CWC15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWC15	NM_016403.4	c.561-463G>A		intron_variant		ENST00000279839.8	NP_057487.2
CWC15	NM_001363371.2	c.561-463G>A		intron_variant			NP_001350300.1
CWC15	NM_001363372.2	c.561-463G>A		intron_variant			NP_001350301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWC15	ENST00000279839.8	c.561-463G>A		intron_variant		1	NM_016403.4	ENSP00000475615.2
CWC15	ENST00000616442.4	n.387-463G>A		intron_variant		2
CWC15	ENST00000621358.4	n.967-463G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121871 AN: 151744 Hom.: 49086 Cov.: 29

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.803 AC: 121949 AN: 151862 Hom.: 49114 Cov.: 29 AF XY: 0.809 AC XY: 60033 AN XY: 74200

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.816

Alfa AF: 0.814 Hom.: 57600

Bravo AF: 0.793

Asia WGS AF: 0.891 AC: 3094 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.39

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: rs7937776; hg19: chr11-94697142;