NM_018294.6:c.1577G>A

Variant names:

• chr10-100233267-C-T
• rs7922946
• NM_018294.6:c.1577G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018294.6(CWF19L1):​c.1577G>A​(p.Arg526Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00124 in 1,613,720 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (10 hom.)
• Consequence: CWF19L1 NM_018294.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.38
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005014986).
• BP6: Variant 10-100233267-C-T is Benign according to our data. Variant chr10-100233267-C-T is described in ClinVar as Benign. ClinVar VariationId is 768383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00631 (960/152130) while in subpopulation AFR AF = 0.022 (913/41502). AF 95% confidence interval is 0.0208. There are 14 homozygotes in GnomAd4. There are 464 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 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.1577G>A	p.Arg526Gln	missense	Exon 14 of 14	NP_060764.3
	CWF19L1	NM_001303404.2		c.1457G>A	p.Arg486Gln	missense	Exon 13 of 13	NP_001290333.1
	CWF19L1	NM_001303405.2		c.1166G>A	p.Arg389Gln	missense	Exon 14 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.1577G>A	p.Arg526Gln	missense	Exon 14 of 14	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.1577G>A	p.Arg526Gln	missense	Exon 14 of 14	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.1574G>A	p.Arg525Gln	missense	Exon 14 of 14	ENSP00000620220.1

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 960 AN: 152014 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00181 AC: 450 AN: 248768 AF XY: 0.00128

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000359

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000712 AC: 1040 AN: 1461590 Hom.: 10 Cov.: 32 AF XY: 0.000597 AC XY: 434 AN XY: 727108

African (AFR) AF: 0.0262 AC: 877 AN: 33474

American (AMR) AF: 0.00105 AC: 47 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5764

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111844

Other (OTH) AF: 0.00142 AC: 86 AN: 60372

GnomAD4 genome AF: 0.00631 AC: 960 AN: 152130 Hom.: 14 Cov.: 32 AF XY: 0.00624 AC XY: 464 AN XY: 74358

African (AFR) AF: 0.0220 AC: 913 AN: 41502

American (AMR) AF: 0.00242 AC: 37 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.00190 AC: 4 AN: 2100

Alfa AF: 0.00272 Hom.: 9

Bravo AF: 0.00705

ESP6500AA AF: 0.0243 AC: 107

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00215 AC: 261

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.4
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.12
Sift	Benign	0.037	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.22
MVP		0.28
MPC		0.59
ClinPred		0.087	T
GERP RS		2.5
Varity_R		0.35
gMVP		0.59
Mutation Taster		=96/4	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: rs7922946; hg19: chr10-101993024; COSMIC: COSV99059467; COSMIC: COSV99059467;