11-94963977-C-T

Variant names:

• chr11-94963977-C-T
• rs7937776
• NM_016403.4:c.561-463G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000299714 (HGNC:):

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 = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWC15	NM_016403.4	c.561-463G>A		intron_variant	Intron 6 of 6	ENST00000279839.8	NP_057487.2
CWC15	NM_001363371.2	c.561-463G>A		intron_variant	Intron 6 of 6		NP_001350300.1
CWC15	NM_001363372.2	c.561-463G>A		intron_variant	Intron 6 of 6		NP_001350301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWC15	ENST00000279839.8	c.561-463G>A		intron_variant	Intron 6 of 6	1	NM_016403.4	ENSP00000475615.2
CWC15	ENST00000616442.4	n.387-463G>A		intron_variant	Intron 2 of 2	2
CWC15	ENST00000621358.4	n.967-463G>A		intron_variant	Intron 5 of 5	5
ENSG00000299714	ENST00000765796.1	n.135+3608C>T		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.740 AC: 30580 AN: 41352

American (AMR) AF: 0.789 AC: 12033 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2733 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4936 AN: 5136

South Asian (SAS) AF: 0.864 AC: 4158 AN: 4814

European-Finnish (FIN) AF: 0.880 AC: 9277 AN: 10540

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55497 AN: 67974

Other (OTH) AF: 0.816 AC: 1722 AN: 2110

Alfa AF: 0.810 Hom.: 74663

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
PhyloP100		-0.13
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: rs7937776; hg19: chr11-94697142;