Genetic Variant NM_018294.6:c.849+123A>G (chr10-100246672-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_018294.6(CWF19L1):c.849+123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 996,910 control chromosomes in the GnomAD database, including 134,240 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 0.55 ( 24154 hom., cov: 33)

Exomes 𝑓: 0.51 ( 110086 hom. )

Consequence

CWF19L1
NM_018294.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

Publications

13 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:

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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 (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018294.6. 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.849+123A>G	intron	N/A	NP_060764.3
CWF19L1	NM_001303404.2		c.849+123A>G	intron	N/A	NP_001290333.1
CWF19L1	NM_001303405.2		c.438+123A>G	intron	N/A	NP_001290334.1	Q69YN2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CWF19L1	ENST00000354105.10	TSL:1 MANE Select	c.849+123A>G	intron	N/A	ENSP00000326411.6	Q69YN2-1
CWF19L1	ENST00000950162.1		c.849+123A>G	intron	N/A	ENSP00000620221.1
CWF19L1	ENST00000950161.1		c.846+126A>G	intron	N/A	ENSP00000620220.1

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

84039

AN:

151940

Hom.:

24122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.716

Gnomad AMI

AF:

0.640

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.534

GnomAD4 exome

AF:

0.506

AC:

427662

AN:

844852

Hom.:

110086

AF XY:

0.502

AC XY:

210990

AN XY:

420298

show subpopulations

African (AFR)

AF:

0.720

AC:

13834

AN:

19202

American (AMR)

AF:

0.404

AC:

6824

AN:

16906

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

6175

AN:

14604

East Asian (EAS)

AF:

0.479

AC:

15044

AN:

31434

South Asian (SAS)

AF:

0.346

AC:

13975

AN:

40394

European-Finnish (FIN)

AF:

0.462

AC:

18313

AN:

39644

Middle Eastern (MID)

AF:

0.459

AC:

1761

AN:

3836

European-Non Finnish (NFE)

AF:

0.518

AC:

332551

AN:

641536

Other (OTH)

AF:

0.514

AC:

19185

AN:

37296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9992

19984

29976

39968

49960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9052

18104

27156

36208

45260

<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:

0.553

AC:

84121

AN:

152058

Hom.:

24154

Cov.:

AF XY:

0.548

AC XY:

40714

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.716

AC:

29717

AN:

41484

American (AMR)

AF:

0.461

AC:

7038

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

1499

AN:

3470

East Asian (EAS)

AF:

0.491

AC:

2542

AN:

5174

South Asian (SAS)

AF:

0.354

AC:

1709

AN:

4822

European-Finnish (FIN)

AF:

0.465

AC:

4902

AN:

10548

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.513

AC:

34849

AN:

67976

Other (OTH)

AF:

0.538

AC:

1136

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1879

3758

5636

7515

9394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.430

Hom.:

1696

Bravo

AF:

0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.20

(source)

DANN

Benign

0.73

PhyloP100

-1.4

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