rs17730369

chr10-100256833-C-Gchr10-100256833-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018294.6(CWF19L1):c.290-357G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,172 control chromosomes in the GnomAD database, including 578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.075 (578 hom., cov: 32)
• Consequence: CWF19L1 NM_018294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CWF19L1	NM_018294.6	c.290-357G>C		intron_variant		ENST00000354105.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWF19L1	ENST00000354105.10	c.290-357G>C		intron_variant		1	NM_018294.6	P1

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11401 AN: 152052 Hom.: 579 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0738

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0750 AC: 11413 AN: 152172 Hom.: 578 Cov.: 32 AF XY: 0.0746 AC XY: 5553 AN XY: 74406

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.0562

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0740

Alfa AF: 0.0115 Hom.: 7

Bravo AF: 0.0771

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs17730369; hg19: chr10-102016590;