Variant 10-100235744-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_018294.6(CWF19L1):c.1395A>C(p.Ala465=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,611,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

CWF19L1
NM_018294.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.33

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 -15 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 10-100235744-T-G is Benign according to our data. Variant chr10-100235744-T-G is described in ClinVar as [Benign]. Clinvar id is 716213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0019 (289/152354) while in subpopulation AFR AF= 0.00676 (281/41586). AF 95% confidence interval is 0.00611. There are 0 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L1	NM_018294.6 linkuse as main transcript	c.1395A>C	p.Ala465=	synonymous_variant	13/14	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.1395A>C	p.Ala465=	synonymous_variant	13/14	1	NM_018294.6	ENSP00000326411	P1	Q69YN2-1
CWF19L1	ENST00000478047.1 linkuse as main transcript	n.1550A>C		non_coding_transcript_exon_variant	4/5	2
CWF19L1	ENST00000468709.5 linkuse as main transcript	c.*945A>C		3_prime_UTR_variant, NMD_transcript_variant	12/13	2		ENSP00000492991
CWF19L1	ENST00000482452.5 linkuse as main transcript	c.*782A>C		3_prime_UTR_variant, NMD_transcript_variant	11/13	5		ENSP00000492899

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00670

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000501

AC:

125

AN:

249716

Hom.:

AF XY:

0.000370

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.00696

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000236

AC:

344

AN:

1459204

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

129

AN XY:

726086

show subpopulations

Gnomad4 AFR exome

AF:

0.00861

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.00190

AC:

289

AN:

152354

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

147

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00676

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000492

Hom.:

Bravo

AF:

0.00215

Asia WGS

AF:

0.000289

AC:

AN:

3478

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	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.1

DANN

Benign

0.78

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