10-100256287-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_018294.6(CWF19L1):c.479G>A(p.Cys160Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,390 control chromosomes in the GnomAD database, including 16,440 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 6337 hom., cov: 32)

Exomes 𝑓: 0.089 ( 10103 hom. )

Consequence

CWF19L1
NM_018294.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.55

Publications

24 publications found

Variant links:

Genes affected

CWF19L1 (HGNC:25613): (CWF19 like cell cycle control factor 1) This gene encodes a member of the CWF19 protein family. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia-17 and mild cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

CWF19L1 links:

CHUK-DT (HGNC:55813): (CHUK divergent transcript)

CHUK-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 10-100256287-C-T is Benign according to our data. Variant chr10-100256287-C-T is described in ClinVar as Benign. ClinVar VariationId is 128879.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L1	NM_018294.6 link	c.479G>A	p.Cys160Tyr	missense_variant	Exon 5 of 14	ENST00000354105.10	NP_060764.3	Q69YN2-1A0A0S2Z5E9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L1	ENST00000354105.10 link	c.479G>A	p.Cys160Tyr	missense_variant	Exon 5 of 14	1	NM_018294.6	ENSP00000326411.6		Q69YN2-1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32097

AN:

151974

Hom.:

6307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0689

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.124

AC:

31163

AN:

251308

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.0749

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0889

AC:

129947

AN:

1461296

Hom.:

10103

Cov.:

AF XY:

0.0885

AC XY:

64312

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.541

AC:

18087

AN:

33452

American (AMR)

AF:

0.123

AC:

5500

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0749

AC:

1957

AN:

26132

East Asian (EAS)

AF:

0.162

AC:

6421

AN:

39694

South Asian (SAS)

AF:

0.130

AC:

11240

AN:

86244

European-Finnish (FIN)

AF:

0.122

AC:

6512

AN:

53410

Middle Eastern (MID)

AF:

0.126

AC:

727

AN:

5766

European-Non Finnish (NFE)

AF:

0.0652

AC:

72472

AN:

1111498

Other (OTH)

AF:

0.116

AC:

7031

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

5441

10882

16323

21764

27205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3088

6176

9264

12352

15440

<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:

0.212

AC:

32182

AN:

152094

Hom.:

6337

Cov.:

AF XY:

0.213

AC XY:

15821

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.525

AC:

21735

AN:

41426

American (AMR)

AF:

0.137

AC:

2099

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

268

AN:

3472

East Asian (EAS)

AF:

0.152

AC:

786

AN:

5182

South Asian (SAS)

AF:

0.140

AC:

676

AN:

4828

European-Finnish (FIN)

AF:

0.130

AC:

1374

AN:

10586

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0688

AC:

4681

AN:

67994

Other (OTH)

AF:

0.186

AC:

392

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

981

1962

2942

3923

4904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.113

Hom.:

8016

Bravo

AF:

0.226

TwinsUK

AF:

0.0601

AC:

223

ALSPAC

AF:

0.0618

AC:

238

ESP6500AA

AF:

0.515

AC:

2270

ESP6500EA

AF:

0.0662

AC:

569

ExAC

AF:

0.130

AC:

15819

Asia WGS

AF:

0.194

AC:

673

AN:

3478

EpiCase

AF:

0.0679

EpiControl

AF:

0.0690

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

CWF19L1-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.00030

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.036

T;T

MetaRNN

Benign

0.00049

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.2

N;.

PhyloP100

1.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.1

N;.

REVEL

Benign

0.042

Sift

Benign

0.27

T;.

Sift4G

Benign

0.12

T;.

Polyphen

0.0

B;.

Vest4

0.035

MPC

0.29

ClinPred

0.013

GERP RS

4.8

Varity_R

0.040

gMVP

0.68

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: 3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over