NM_018294.6:c.1045-2713G>A

Variant names:

• chr10-100240944-C-T
• rs17668255
• NM_018294.6:c.1045-2713G>A

Variant summary

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

The NM_018294.6(CWF19L1):​c.1045-2713G>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
• Publications: 14 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=-0.91).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	NM_018294.6	MANE Select	c.1045-2713G>A		intron	N/A	NP_060764.3
	CWF19L1	NM_001303404.2		c.1045-2713G>A		intron	N/A	NP_001290333.1
	CWF19L1	NM_001303405.2		c.634-2713G>A		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.1045-2713G>A		intron	N/A	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.1045-2713G>A		intron	N/A	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.1042-2713G>A		intron	N/A	ENSP00000620220.1

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

African (AFR) AF: 0.0888 AC: 3591 AN: 40426

American (AMR) AF: 0.295 AC: 4440 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1081 AN: 3462

East Asian (EAS) AF: 0.0665 AC: 341 AN: 5130

South Asian (SAS) AF: 0.157 AC: 750 AN: 4774

European-Finnish (FIN) AF: 0.323 AC: 3293 AN: 10200

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.428 AC: 29018 AN: 67820

Other (OTH) AF: 0.309 AC: 643 AN: 2080

Alfa AF: 0.385 Hom.: 11690

Bravo AF: 0.278

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.60
PhyloP100		-0.25
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: rs17668255; hg19: chr10-102000701;