Genetic Variant NM_016403.4: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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016403.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CWC15	NM_016403.4	MANE Select	c.441+104A>G	intron	N/A	NP_057487.2	Q9P013
CWC15	NM_001363371.2		c.441+104A>G	intron	N/A	NP_001350300.1	Q9P013
CWC15	NM_001363372.2		c.441+104A>G	intron	N/A	NP_001350301.1	Q9P013

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CWC15	ENST00000279839.8	TSL:1 MANE Select	c.441+104A>G	intron	N/A	ENSP00000475615.2	Q9P013
CWC15	ENST00000884097.1		c.441+104A>G	intron	N/A	ENSP00000554156.1
CWC15	ENST00000884093.1		c.441+104A>G	intron	N/A	ENSP00000554152.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over