rs4919438

Positions:

• chr10-100246672-T-C
• chr10-100246672-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018294.6(CWF19L1):​c.849+123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 996,910 control chromosomes in the GnomAD database, including 134,240 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 0.55 (24154 hom., cov: 33)
  • Exomes 𝑓: 0.51 (110086 hom.)
• Consequence: CWF19L1 NM_018294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L1	NM_018294.6	c.849+123A>G		intron_variant		ENST00000354105.10	NP_060764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWF19L1	ENST00000354105.10	c.849+123A>G		intron_variant		1	NM_018294.6	ENSP00000326411	P1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84039 AN: 151940 Hom.: 24122 Cov.: 33

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.534

GnomAD4 exome AF: 0.506 AC: 427662 AN: 844852 Hom.: 110086 AF XY: 0.502 AC XY: 210990 AN XY: 420298

Gnomad4 AFR exome AF: 0.720

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.553 AC: 84121 AN: 152058 Hom.: 24154 Cov.: 33 AF XY: 0.548 AC XY: 40714 AN XY: 74324

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.538

Alfa AF: 0.414 Hom.: 1499

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.73

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: rs4919438; hg19: chr10-102006429; COSMIC: COSV62498982; COSMIC: COSV62498982;