Genetic Variant CWF19L1:c.-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 ENST00000905383.1(CWF19L1):c.-57G>A variant causes a 5 prime UTR 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
ENST00000905383.1 5_prime_UTR

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

CWF19L1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000905383.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000905383.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CWF19L1	NM_018294.6	MANE Select	c.-57G>A	upstream_gene	N/A	NP_060764.3
CWF19L1	NM_001303404.2		c.-57G>A	upstream_gene	N/A	NP_001290333.1
CWF19L1	NM_001303405.2		c.-513G>A	upstream_gene	N/A	NP_001290334.1	Q69YN2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CWF19L1	ENST00000905383.1		c.-57G>A	5_prime_UTR	Exon 1 of 13	ENSP00000575442.1
CWF19L1	ENST00000950160.1		c.-57G>A	5_prime_UTR	Exon 1 of 12	ENSP00000620219.1
CWF19L1	ENST00000473842.1	TSL:5	c.-57G>A	5_prime_UTR	Exon 1 of 6	ENSP00000493150.1	A0A286YF56

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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