Variant 10-100233267-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018294.6(CWF19L1):c.1577G>A(p.Arg526Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00124 in 1,613,720 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0063 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 10 hom. )

Consequence

CWF19L1
NM_018294.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.38

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005014986).

BP6

Variant 10-100233267-C-T is Benign according to our data. Variant chr10-100233267-C-T is described in ClinVar as [Benign]. Clinvar id is 768383.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00631 (960/152130) while in subpopulation AFR AF= 0.022 (913/41502). AF 95% confidence interval is 0.0208. There are 14 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L1	NM_018294.6 linkuse as main transcript	c.1577G>A	p.Arg526Gln	missense_variant	14/14	ENST00000354105.10	NP_060764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWF19L1	ENST00000354105.10 linkuse as main transcript	c.1577G>A	p.Arg526Gln	missense_variant	14/14	1	NM_018294.6	ENSP00000326411	P1	Q69YN2-1
CHUK-DT	ENST00000667469.1 linkuse as main transcript	n.245C>T		non_coding_transcript_exon_variant	3/4

Frequencies

GnomAD3 genomes

AF:

0.00632

AC:

960

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00181

AC:

450

AN:

248768

Hom.:

AF XY:

0.00128

AC XY:

173

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.0253

Gnomad AMR exome

AF:

0.000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.000712

AC:

1040

AN:

1461590

Hom.:

Cov.:

AF XY:

0.000597

AC XY:

434

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0262

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00631

AC:

960

AN:

152130

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

464

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00705

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00215

AC:

261

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.025

Eigen

Benign

0.15

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0050

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.12

Sift

Benign

0.037

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.22

MVP

0.28

MPC

0.59

ClinPred

0.087

GERP RS

2.5

Varity_R

0.35

gMVP

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over