Variant chr10-100235720-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018294.6(CWF19L1):c.1419A>C(p.Thr473=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,612,474 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

CWF19L1
NM_018294.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.899

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-100235720-T-G is Benign according to our data. Variant chr10-100235720-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 715239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.899 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000906 (138/152348) while in subpopulation NFE AF= 0.00168 (114/68042). AF 95% confidence interval is 0.00143. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CWF19L1	NM_018294.6 linkuse as main transcript	c.1419A>C	p.Thr473=	synonymous_variant	13/14	ENST00000354105.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWF19L1	ENST00000354105.10 linkuse as main transcript	c.1419A>C	p.Thr473=	synonymous_variant	13/14	1	NM_018294.6	P1	Q69YN2-1
CWF19L1	ENST00000478047.1 linkuse as main transcript	n.1574A>C		non_coding_transcript_exon_variant	4/5	2
CWF19L1	ENST00000468709.5 linkuse as main transcript	c.*969A>C		3_prime_UTR_variant, NMD_transcript_variant	12/13	2
CWF19L1	ENST00000482452.5 linkuse as main transcript	c.*806A>C		3_prime_UTR_variant, NMD_transcript_variant	11/13	5

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00168

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000852

AC:

213

AN:

250080

Hom.:

AF XY:

0.000872

AC XY:

118

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000681

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00140

AC:

2042

AN:

1460126

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1003

AN XY:

726466

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000907

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.000961

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152348

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00168

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000842

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00115

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	CWF19L1: BP4, BP7 -

CWF19L1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.3

DANN

Benign

0.80

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