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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000473842.1(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
ENST00000473842.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.100

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AFR exome

AF:

0.0971

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.0507

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.440

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.296

AC:

45009

AN:

152140

Hom.:

8154

Cov.:

AF XY:

0.289

AC XY:

21482

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.300

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.0649

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.325

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.394

Hom.:

24238

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

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over