rs17729876

Variant names:

• chr10-100239989-G-A
• rs17729876
• NM_018294.6:c.1045-1758C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018294.6(CWF19L1):​c.1045-1758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,124 control chromosomes in the GnomAD database, including 8,049 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 (8049 hom., cov: 32)
• Consequence: CWF19L1 NM_018294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 13 publications found

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]

CHUK-DT (HGNC:55813): (CHUK divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018294.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	NM_018294.6	MANE Select	c.1045-1758C>T		intron	N/A	NP_060764.3
	CWF19L1	NM_001303404.2		c.1045-1758C>T		intron	N/A	NP_001290333.1
	CWF19L1	NM_001303405.2		c.634-1758C>T		intron	N/A	NP_001290334.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	ENST00000354105.10	TSL:1 MANE Select	c.1045-1758C>T		intron	N/A	ENSP00000326411.6
	CWF19L1	ENST00000466408.1	TSL:2	n.399-1758C>T		intron	N/A
	CWF19L1	ENST00000466955.5	TSL:3	n.586-1758C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44028 AN: 152006 Hom.: 8051 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.289 AC: 44017 AN: 152124 Hom.: 8049 Cov.: 32 AF XY: 0.283 AC XY: 21003 AN XY: 74346

African (AFR) AF: 0.0885 AC: 3677 AN: 41546

American (AMR) AF: 0.297 AC: 4538 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3470

East Asian (EAS) AF: 0.0645 AC: 334 AN: 5176

South Asian (SAS) AF: 0.156 AC: 753 AN: 4818

European-Finnish (FIN) AF: 0.326 AC: 3438 AN: 10546

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29098 AN: 67980

Other (OTH) AF: 0.309 AC: 651 AN: 2110

Alfa AF: 0.342 Hom.: 3925

Bravo AF: 0.278

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.65
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17729876; hg19: chr10-101999746;