10-100256833-C-G

Variant names:

• chr10-100256833-C-G
• rs17730369
• NM_018294.6:c.290-357G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.136 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	NM_018294.6	MANE Select	c.290-357G>C		intron	N/A	NP_060764.3
	CWF19L1	NM_001303404.2		c.290-357G>C		intron	N/A	NP_001290333.1
	CWF19L1	NM_001303405.2		c.-122-357G>C		intron	N/A	NP_001290334.1	Q69YN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	ENST00000354105.10	TSL:1 MANE Select	c.290-357G>C		intron	N/A	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.290-357G>C		intron	N/A	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.290-357G>C		intron	N/A	ENSP00000620220.1

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

African (AFR) AF: 0.139 AC: 5782 AN: 41506

American (AMR) AF: 0.0524 AC: 800 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.0562 AC: 291 AN: 5180

South Asian (SAS) AF: 0.0651 AC: 314 AN: 4826

European-Finnish (FIN) AF: 0.0550 AC: 583 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3211 AN: 67998

Other (OTH) AF: 0.0740 AC: 156 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		-0.11
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: rs17730369; hg19: chr10-102016590;