Genetic Variant CWF19L1:n.-57G>A (chr10-100267650-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000468709.5(CWF19L1):n.-57G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,606,636 control chromosomes in the GnomAD database, including 126,679 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 0.30 ( 8154 hom., cov: 32)

Exomes 𝑓: 0.39 ( 118525 hom. )

Consequence

CWF19L1
ENST00000468709.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.100

Publications

35 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 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 17
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

CWF19L1 links:

Genome browser will be placed here

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=-0.58).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L1	NM_018294.6 link	c.-57G>A		upstream_gene_variant		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.-57G>A		upstream_gene_variant		1	NM_018294.6	ENSP00000326411.6		Q69YN2-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

45017

AN:

152022

Hom.:

8156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.0654

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.309

GnomAD4 exome

AF:

0.388

AC:

564803

AN:

1454496

Hom.:

118525

Cov.:

AF XY:

0.383

AC XY:

277271

AN XY:

724066

show subpopulations

African (AFR)

AF:

0.0971

AC:

3230

AN:

33280

American (AMR)

AF:

0.234

AC:

10445

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

8062

AN:

26060

East Asian (EAS)

AF:

0.0507

AC:

2011

AN:

39642

South Asian (SAS)

AF:

0.158

AC:

13601

AN:

86060

European-Finnish (FIN)

AF:

0.331

AC:

17644

AN:

53356

Middle Eastern (MID)

AF:

0.270

AC:

1553

AN:

5744

European-Non Finnish (NFE)

AF:

0.440

AC:

486921

AN:

1105540

Other (OTH)

AF:

0.355

AC:

21336

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

16413

32826

49239

65652

82065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14250

28500

42750

57000

71250

<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:

0.296

AC:

45009

AN:

152140

Hom.:

8154

Cov.:

AF XY:

0.289

AC XY:

21482

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.111

AC:

4619

AN:

41512

American (AMR)

AF:

0.300

AC:

4593

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1084

AN:

3468

East Asian (EAS)

AF:

0.0649

AC:

337

AN:

5190

South Asian (SAS)

AF:

0.156

AC:

753

AN:

4824

European-Finnish (FIN)

AF:

0.325

AC:

3434

AN:

10576

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29087

AN:

67962

Other (OTH)

AF:

0.310

AC:

653

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1510

3020

4530

6040

7550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.372

Hom.:

36768

Bravo

AF:

0.285

Asia WGS

AF:

0.115

AC:

400

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.1

(source)

DANN

Benign

0.70

PhyloP100

-0.10

PromoterAI

0.017

Neutral

(source)

Mutation Taster

=300/0

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