Variant chr10-100236976-G-T 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.1255-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,566,940 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 9 hom. )

Consequence

CWF19L1
NM_018294.6 splice_region, intron

Scores

Splicing: ADA: 0.0002202

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.348

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:

CWF19L1 (HGNC:):

CWF19L1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-100236976-G-T is Benign according to our data. Variant chr10-100236976-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 787543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-100236976-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00211 (322/152282) while in subpopulation NFE AF= 0.00403 (274/68026). AF 95% confidence interval is 0.00364. There are 0 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L1	NM_018294.6 linkuse as main transcript	c.1255-7C>A		splice_region_variant, intron_variant		ENST00000354105.10	NP_060764.3	Q69YN2-1A0A0S2Z5E9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CWF19L1	ENST00000354105.10 linkuse as main transcript	c.1255-7C>A	splice_region_variant, intron_variant	1	NM_018294.6	ENSP00000326411.6	Q69YN2-1
CWF19L1	ENST00000468709.5 linkuse as main transcript	n.*805-7C>A	splice_region_variant, intron_variant	2		ENSP00000492991.1	A0A0S2Z5Q6
CWF19L1	ENST00000478047.1 linkuse as main transcript	n.1410-7C>A	splice_region_variant, intron_variant	2
CWF19L1	ENST00000482452.5 linkuse as main transcript	n.*642-7C>A	splice_region_variant, intron_variant	5		ENSP00000492899.1	A0A286YEP9

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00403

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00169

AC:

359

AN:

212072

Hom.:

AF XY:

0.00180

AC XY:

205

AN XY:

113972

show subpopulations

Gnomad AFR exome

AF:

0.000381

Gnomad AMR exome

AF:

0.000307

Gnomad ASJ exome

AF:

0.000150

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00137

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00312

AC:

4411

AN:

1414658

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

2152

AN XY:

699742

show subpopulations

Gnomad4 AFR exome

AF:

0.000411

Gnomad4 AMR exome

AF:

0.000389

Gnomad4 ASJ exome

AF:

0.000215

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.000977

Gnomad4 NFE exome

AF:

0.00378

Gnomad4 OTH exome

AF:

0.00350

GnomAD4 genome

AF:

0.00211

AC:

322

AN:

152282

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

129

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00403

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.00229

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	CWF19L1: BP4, BS2 -
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

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.6

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.060

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