rs7924284

Variant names:

• chr10-100258332-C-T
• rs7924284
• NM_018294.6:c.290-1856G>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.290-1856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,112 control chromosomes in the GnomAD database, including 6,331 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 0.21 (6331 hom., cov: 31)
• Consequence: CWF19L1 NM_018294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• 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)

RNU6-422P (HGNC:47385): (RNA, U6 small nuclear 422, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L1	NM_018294.6	c.290-1856G>A		intron_variant	Intron 4 of 13	ENST00000354105.10	NP_060764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L1	ENST00000354105.10	c.290-1856G>A		intron_variant	Intron 4 of 13	1	NM_018294.6	ENSP00000326411.6

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32105 AN: 151994 Hom.: 6301 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.212 AC: 32190 AN: 152112 Hom.: 6331 Cov.: 31 AF XY: 0.213 AC XY: 15829 AN XY: 74396

African (AFR) AF: 0.525 AC: 21733 AN: 41428

American (AMR) AF: 0.138 AC: 2103 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3470

East Asian (EAS) AF: 0.150 AC: 778 AN: 5170

South Asian (SAS) AF: 0.140 AC: 675 AN: 4824

European-Finnish (FIN) AF: 0.130 AC: 1382 AN: 10600

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0689 AC: 4686 AN: 68012

Other (OTH) AF: 0.186 AC: 394 AN: 2114

Alfa AF: 0.106 Hom.: 3135

Bravo AF: 0.226

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		-0.099
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: rs7924284; hg19: chr10-102018089;