rs117713471

Variant names:

• chr10-100233333-T-A
• rs117713471
• NM_018294.6:c.1511A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-100233333-T-A
• chr10-100233333-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018294.6(CWF19L1):​c.1511A>T​(p.Asp504Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,882 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (16 hom.)
• Consequence: CWF19L1 NM_018294.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.97
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052903593).
• BP6: Variant 10-100233333-T-A is Benign according to our data. Variant chr10-100233333-T-A is described in ClinVar as Benign. ClinVar VariationId is 708368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00139 (211/152158) while in subpopulation EAS AF = 0.0328 (169/5156). AF 95% confidence interval is 0.0287. There are 1 homozygotes in GnomAd4. There are 113 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 16 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.1511A>T	p.Asp504Val	missense	Exon 14 of 14	NP_060764.3
	CWF19L1	NM_001303404.2		c.1391A>T	p.Asp464Val	missense	Exon 13 of 13	NP_001290333.1
	CWF19L1	NM_001303405.2		c.1100A>T	p.Asp367Val	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.1511A>T	p.Asp504Val	missense	Exon 14 of 14	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.1511A>T	p.Asp504Val	missense	Exon 14 of 14	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.1508A>T	p.Asp503Val	missense	Exon 14 of 14	ENSP00000620220.1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152040 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00282 AC: 701 AN: 248848 AF XY: 0.00265

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.0325

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000270

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.00100 AC: 1469 AN: 1461724 Hom.: 16 Cov.: 32 AF XY: 0.00101 AC XY: 732 AN XY: 727158

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00253 AC: 66 AN: 26130

East Asian (EAS) AF: 0.0267 AC: 1058 AN: 39698

South Asian (SAS) AF: 0.00122 AC: 105 AN: 86222

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53412

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1111928

Other (OTH) AF: 0.00200 AC: 121 AN: 60394

GnomAD4 genome AF: 0.00139 AC: 211 AN: 152158 Hom.: 1 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74396

African (AFR) AF: 0.00 AC: 0 AN: 41510

American (AMR) AF: 0.000327 AC: 5 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.0328 AC: 169 AN: 5156

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67990

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00125 Hom.: 1

Bravo AF: 0.00174

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00276 AC: 335

Asia WGS AF: 0.0160 AC: 56 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.0
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.20
Sift	Benign	0.031	D
Sift4G	Benign	0.13	T
Polyphen		0.27	B
Vest4		0.28
MVP		0.42
MPC		0.43
ClinPred		0.12	T
GERP RS		4.2
Varity_R		0.34
gMVP		0.53
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: rs117713471; hg19: chr10-101993090; COSMIC: COSV62499334; COSMIC: COSV62499334;