Variant chr10-100233333-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018294.6(CWF19L1):c.1511A>T(p.Asp504Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,882 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

CWF19L1
NM_018294.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.97

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052903593).

BP6

Variant 10-100233333-T-A is Benign according to our data. Variant chr10-100233333-T-A is described in ClinVar as [Benign]. Clinvar id is 708368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00139 (211/152158) while in subpopulation EAS AF= 0.0328 (169/5156). AF 95% confidence interval is 0.0287. There are 1 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CWF19L1	NM_018294.6 linkuse as main transcript	c.1511A>T	p.Asp504Val	missense_variant	14/14	ENST00000354105.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWF19L1	ENST00000354105.10 linkuse as main transcript	c.1511A>T	p.Asp504Val	missense_variant	14/14	1	NM_018294.6	P1	Q69YN2-1
CHUK-DT	ENST00000667469.1 linkuse as main transcript	n.311T>A		non_coding_transcript_exon_variant	3/4

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0327

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00282

AC:

701

AN:

248848

Hom.:

AF XY:

0.00265

AC XY:

357

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.0325

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000270

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.00100

AC:

1469

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

732

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.0267

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.0000962

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152158

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0328

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.00174

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00276

AC:

335

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.023

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.20

Sift

Benign

0.031

Sift4G

Benign

0.13

Polyphen

0.27

Vest4

0.28

MVP

0.42

MPC

0.43

ClinPred

0.12

GERP RS

4.2

Varity_R

0.34

gMVP

0.53

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