10-100246672-T-C

Variant names:

• chr10-100246672-T-C
• rs4919438
• NM_018294.6:c.849+123A>G

Variant summary

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

The ENST00000354105.10(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 ENST00000354105.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354105.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	NM_018294.6	MANE Select	c.849+123A>G		intron	N/A	NP_060764.3
	CWF19L1	NM_001303404.2		c.849+123A>G		intron	N/A	NP_001290333.1
	CWF19L1	NM_001303405.2		c.438+123A>G		intron	N/A	NP_001290334.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	ENST00000354105.10	TSL:1 MANE Select	c.849+123A>G		intron	N/A	ENSP00000326411.6
	CWF19L1	ENST00000466955.5	TSL:3	n.390+123A>G		intron	N/A
	CWF19L1	ENST00000468709.5	TSL:2	n.*399+123A>G		intron	N/A	ENSP00000492991.1

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

African (AFR) AF: 0.720 AC: 13834 AN: 19202

American (AMR) AF: 0.404 AC: 6824 AN: 16906

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 6175 AN: 14604

East Asian (EAS) AF: 0.479 AC: 15044 AN: 31434

South Asian (SAS) AF: 0.346 AC: 13975 AN: 40394

European-Finnish (FIN) AF: 0.462 AC: 18313 AN: 39644

Middle Eastern (MID) AF: 0.459 AC: 1761 AN: 3836

European-Non Finnish (NFE) AF: 0.518 AC: 332551 AN: 641536

Other (OTH) AF: 0.514 AC: 19185 AN: 37296

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

African (AFR) AF: 0.716 AC: 29717 AN: 41484

American (AMR) AF: 0.461 AC: 7038 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2542 AN: 5174

South Asian (SAS) AF: 0.354 AC: 1709 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4902 AN: 10548

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34849 AN: 67976

Other (OTH) AF: 0.538 AC: 1136 AN: 2112

Alfa AF: 0.430 Hom.: 1696

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.73
PhyloP100		-1.4
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: rs4919438; hg19: chr10-102006429; COSMIC: COSV62498982; COSMIC: COSV62498982;