chr10-100250223-T-C

Position:

• chr10-100250223-T-C

Variant summary

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

The NM_018294.6(CWF19L1):​c.708+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 1,463,114 control chromosomes in the GnomAD database, including 2,645 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 (582 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2063 hom.)
• Consequence: CWF19L1 NM_018294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L1	NM_018294.6	c.708+25A>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.708+25A>G		intron_variant		1	NM_018294.6	ENSP00000326411	P1

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11407 AN: 152136 Hom.: 583 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0723

GnomAD3 exomes AF: 0.0547 AC: 13693 AN: 250208 Hom.: 473 AF XY: 0.0533 AC XY: 7207 AN XY: 135330

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0466

Gnomad ASJ exome AF: 0.0559

Gnomad EAS exome AF: 0.0523

Gnomad SAS exome AF: 0.0618

Gnomad FIN exome AF: 0.0495

Gnomad NFE exome AF: 0.0442

Gnomad OTH exome AF: 0.0506

GnomAD4 exome AF: 0.0518 AC: 67840 AN: 1310858 Hom.: 2063 Cov.: 20 AF XY: 0.0512 AC XY: 33811 AN XY: 660632

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.0548

Gnomad4 EAS exome AF: 0.0650

Gnomad4 SAS exome AF: 0.0582

Gnomad4 FIN exome AF: 0.0508

Gnomad4 NFE exome AF: 0.0476

Gnomad4 OTH exome AF: 0.0609

GnomAD4 genome AF: 0.0750 AC: 11419 AN: 152256 Hom.: 582 Cov.: 32 AF XY: 0.0746 AC XY: 5557 AN XY: 74454

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0527

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.0644

Gnomad4 FIN AF: 0.0554

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0725

Alfa AF: 0.0528 Hom.: 139

Bravo AF: 0.0771

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7072367; hg19: chr10-102009980;