rs7073610

Variant names:

• chr10-100246868-G-A
• rs7073610
• NM_018294.6:c.776C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018294.6(CWF19L1):​c.776C>T​(p.Pro259Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,613,678 control chromosomes in the GnomAD database, including 2,439 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (350 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2089 hom.)
• Consequence: CWF19L1 NM_018294.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.56
• Publications: 29 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=0.0028273463).
• BP6: Variant 10-100246868-G-A is Benign according to our data. Variant chr10-100246868-G-A is described in ClinVar as Benign. ClinVar VariationId is 128881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L1	NM_018294.6	c.776C>T	p.Pro259Leu	missense_variant	Exon 8 of 14	ENST00000354105.10	NP_060764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L1	ENST00000354105.10	c.776C>T	p.Pro259Leu	missense_variant	Exon 8 of 14	1	NM_018294.6	ENSP00000326411.6

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9609 AN: 152058 Hom.: 350 Cov.: 33

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0670

GnomAD2 exomes AF: 0.0516 AC: 12983 AN: 251384 AF XY: 0.0509

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.0559

Gnomad EAS exome AF: 0.0523

Gnomad FIN exome AF: 0.0499

Gnomad NFE exome AF: 0.0440

Gnomad OTH exome AF: 0.0497

GnomAD4 exome AF: 0.0508 AC: 74267 AN: 1461502 Hom.: 2089 Cov.: 31 AF XY: 0.0506 AC XY: 36780 AN XY: 727064

African (AFR) AF: 0.101 AC: 3378 AN: 33468

American (AMR) AF: 0.0456 AC: 2037 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0546 AC: 1426 AN: 26122

East Asian (EAS) AF: 0.0647 AC: 2568 AN: 39692

South Asian (SAS) AF: 0.0579 AC: 4994 AN: 86206

European-Finnish (FIN) AF: 0.0518 AC: 2765 AN: 53416

Middle Eastern (MID) AF: 0.0491 AC: 283 AN: 5768

European-Non Finnish (NFE) AF: 0.0479 AC: 53301 AN: 1111744

Other (OTH) AF: 0.0582 AC: 3515 AN: 60374

GnomAD4 genome AF: 0.0632 AC: 9616 AN: 152176 Hom.: 350 Cov.: 33 AF XY: 0.0634 AC XY: 4714 AN XY: 74410

African (AFR) AF: 0.0977 AC: 4059 AN: 41526

American (AMR) AF: 0.0487 AC: 743 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3472

East Asian (EAS) AF: 0.0558 AC: 289 AN: 5178

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4822

European-Finnish (FIN) AF: 0.0556 AC: 589 AN: 10588

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3208 AN: 68004

Other (OTH) AF: 0.0664 AC: 140 AN: 2110

Alfa AF: 0.0507 Hom.: 1001

Bravo AF: 0.0643

TwinsUK AF: 0.0453 AC: 168

ALSPAC AF: 0.0467 AC: 180

ESP6500AA AF: 0.0953 AC: 420

ESP6500EA AF: 0.0463 AC: 398

ExAC AF: 0.0526 AC: 6388

Asia WGS AF: 0.0820 AC: 285 AN: 3478

EpiCase AF: 0.0440

EpiControl AF: 0.0436

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.056
Sift	Benign	0.31	T
Sift4G	Benign	0.35	T
Polyphen		0.050	B
Vest4		0.087
MPC		0.18
ClinPred		0.031	T
GERP RS		4.6
Varity_R		0.083
gMVP		0.30
Mutation Taster		=81/19	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: rs7073610; hg19: chr10-102006625; COSMIC: COSV62499001; COSMIC: COSV62499001;