11-94969885-T-C

Variant names:

• chr11-94969885-T-C
• rs7107185
• NM_016403.4:c.441+104A>G

Variant summary

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

The NM_016403.4(CWC15):​c.441+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 575,498 control chromosomes in the GnomAD database, including 71,920 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 0.46 (16946 hom., cov: 32)
  • Exomes 𝑓: 0.50 (54974 hom.)
• Consequence: CWC15 NM_016403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWC15	NM_016403.4	c.441+104A>G		intron_variant	Intron 5 of 6	ENST00000279839.8	NP_057487.2
CWC15	NM_001363371.2	c.441+104A>G		intron_variant	Intron 5 of 6		NP_001350300.1
CWC15	NM_001363372.2	c.441+104A>G		intron_variant	Intron 5 of 6		NP_001350301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWC15	ENST00000279839.8	c.441+104A>G		intron_variant	Intron 5 of 6	1	NM_016403.4	ENSP00000475615.2
CWC15	ENST00000616442.4	n.267+104A>G		intron_variant	Intron 1 of 2	2
CWC15	ENST00000621358.4	n.847+104A>G		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70662 AN: 151890 Hom.: 16943 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.503 AC: 212863 AN: 423490 Hom.: 54974 AF XY: 0.501 AC XY: 110070 AN XY: 219622

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.299

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.465 AC: 70674 AN: 152008 Hom.: 16946 Cov.: 32 AF XY: 0.463 AC XY: 34382 AN XY: 74288

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.481

Alfa AF: 0.489 Hom.: 2649

Bravo AF: 0.454

Asia WGS AF: 0.326 AC: 1136 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.40

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: rs7107185; hg19: chr11-94703049;