rs17668255

Positions:

• chr10-100240944-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.1045-2713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 150,116 control chromosomes in the GnomAD database, including 7,953 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 0.29 (7953 hom., cov: 28)
• Consequence: CWF19L1 NM_018294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L1	NM_018294.6	c.1045-2713G>A		intron_variant		ENST00000354105.10	NP_060764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWF19L1	ENST00000354105.10	c.1045-2713G>A		intron_variant		1	NM_018294.6	ENSP00000326411	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 43609 AN: 150028 Hom.: 7955 Cov.: 28

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.290 AC: 43599 AN: 150116 Hom.: 7953 Cov.: 28 AF XY: 0.283 AC XY: 20724 AN XY: 73186

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0665

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.309

Alfa AF: 0.405 Hom.: 9674

Bravo AF: 0.278

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.60

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: rs17668255; hg19: chr10-102000701;