NM_018294.6:c.1419A>C

Variant names:

• chr10-100235720-T-G
• rs139693285
• NM_018294.6:c.1419A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018294.6(CWF19L1):​c.1419A>C​(p.Thr473Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,612,474 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: CWF19L1 NM_018294.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.899
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 10-100235720-T-G is Benign according to our data. Variant chr10-100235720-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 715239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.899 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000906 (138/152348) while in subpopulation NFE AF = 0.00168 (114/68042). AF 95% confidence interval is 0.00143. There are 0 homozygotes in GnomAd4. There are 68 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.1419A>C	p.Thr473Thr	synonymous	Exon 13 of 14	NP_060764.3
	CWF19L1	NM_001303404.2		c.1299A>C	p.Thr433Thr	synonymous	Exon 12 of 13	NP_001290333.1
	CWF19L1	NM_001303405.2		c.1008A>C	p.Thr336Thr	synonymous	Exon 13 of 14	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.1419A>C	p.Thr473Thr	synonymous	Exon 13 of 14	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.1419A>C	p.Thr473Thr	synonymous	Exon 13 of 14	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.1416A>C	p.Thr472Thr	synonymous	Exon 13 of 14	ENSP00000620220.1

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000852 AC: 213 AN: 250080 AF XY: 0.000872

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000681

Gnomad NFE exome AF: 0.00158

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00140 AC: 2042 AN: 1460126 Hom.: 2 Cov.: 29 AF XY: 0.00138 AC XY: 1003 AN XY: 726466

African (AFR) AF: 0.000179 AC: 6 AN: 33478

American (AMR) AF: 0.000335 AC: 15 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.000907 AC: 47 AN: 51844

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00172 AC: 1914 AN: 1111878

Other (OTH) AF: 0.000961 AC: 58 AN: 60372

GnomAD4 genome AF: 0.000906 AC: 138 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000913 AC XY: 68 AN XY: 74500

African (AFR) AF: 0.000313 AC: 13 AN: 41574

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00168 AC: 114 AN: 68042

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.000842

Asia WGS AF: 0.000289 AC: 1 AN: 3476

EpiCase AF: 0.00115

EpiControl AF: 0.00142

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CWF19L1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.3
DANN	Benign	0.80
PhyloP100		-0.90
Mutation Taster		=97/3	polymorphism

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: rs139693285; hg19: chr10-101995477;