Genetic Variant CWC15:c.441+104A>G (chr11-94969885-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

7 publications found

Variant links:

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 links:

ENSG00000299714 (HGNC:):

ENSG00000299714 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
CWC15	NM_016403.4 link	c.441+104A>G	intron_variant	Intron 5 of 6	ENST00000279839.8	NP_057487.2
CWC15	NM_001363371.2 link	c.441+104A>G	intron_variant	Intron 5 of 6		NP_001350300.1
CWC15	NM_001363372.2 link	c.441+104A>G	intron_variant	Intron 5 of 6		NP_001350301.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CWC15	ENST00000279839.8 link	c.441+104A>G	intron_variant	Intron 5 of 6	1	NM_016403.4	ENSP00000475615.2
CWC15	ENST00000616442.4 link	n.267+104A>G	intron_variant	Intron 1 of 2	2
CWC15	ENST00000621358.4 link	n.847+104A>G	intron_variant	Intron 4 of 5	5
ENSG00000299714	ENST00000765796.1 link	n.136-149T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70662

AN:

151890

Hom.:

16943

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.383

AC:

3930

AN:

10260

American (AMR)

AF:

0.398

AC:

4335

AN:

10888

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

5584

AN:

11826

East Asian (EAS)

AF:

0.299

AC:

7844

AN:

26256

South Asian (SAS)

AF:

0.437

AC:

10872

AN:

24856

European-Finnish (FIN)

AF:

0.526

AC:

16617

AN:

31574

Middle Eastern (MID)

AF:

0.489

AC:

851

AN:

1740

European-Non Finnish (NFE)

AF:

0.536

AC:

151524

AN:

282838

Other (OTH)

AF:

0.486

AC:

11306

AN:

23252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4973

9947

14920

19894

24867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1952

3904

5856

7808

9760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.465

AC:

70674

AN:

152008

Hom.:

16946

Cov.:

AF XY:

0.463

AC XY:

34382

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.379

AC:

15720

AN:

41450

American (AMR)

AF:

0.444

AC:

6784

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

1667

AN:

3470

East Asian (EAS)

AF:

0.238

AC:

1233

AN:

5176

South Asian (SAS)

AF:

0.427

AC:

2056

AN:

4816

European-Finnish (FIN)

AF:

0.515

AC:

5429

AN:

10546

Middle Eastern (MID)

AF:

0.517

AC:

151

AN:

292

European-Non Finnish (NFE)

AF:

0.530

AC:

36011

AN:

67942

Other (OTH)

AF:

0.481

AC:

1015

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1925

3850

5774

7699

9624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.486

Hom.:

2714

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

(source)

DANN

Benign

0.40

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over