11-66566127-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003793.4(CTSF):c.762G>A(p.Arg254Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,613,860 control chromosomes in the GnomAD database, including 244,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 29705 hom., cov: 32)

Exomes 𝑓: 0.54 ( 214603 hom. )

Consequence

CTSF
NM_003793.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.259

Publications

27 publications found

Variant links:

Genes affected

CTSF (HGNC:2531): (cathepsin F) Cathepsins are papain family cysteine proteinases that represent a major component of the lysosomal proteolytic system. Cathepsins generally contain a signal sequence, followed by a propeptide and then a catalytically active mature region. The very long (251 amino acid residues) proregion of the cathepsin F precursor contains a C-terminal domain similar to the pro-segment of cathepsin L-like enzymes, a 50-residue flexible linker peptide, and an N-terminal domain predicted to adopt a cystatin-like fold. The cathepsin F proregion is unique within the papain family cysteine proteases in that it contains this additional N-terminal segment predicted to share structural similarities with cysteine protease inhibitors of the cystatin superfamily. This cystatin-like domain contains some of the elements known to be important for inhibitory activity. CTSF encodes a predicted protein of 484 amino acids which contains a 19 residue signal peptide. Cathepsin F contains five potential N-glycosylation sites, and it may be targeted to the endosomal/lysosomal compartment via the mannose 6-phosphate receptor pathway. The cathepsin F gene is ubiquitously expressed, and it maps to chromosome 11q13, close to the gene encoding cathepsin W. [provided by RefSeq, Jul 2008]

CTSF Gene-Disease associations (from GenCC):

adult neuronal ceroid lipofuscinosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuronal ceroid lipofuscinosis 13
Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

CTSF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.062).

BP6

Variant 11-66566127-C-T is Benign according to our data. Variant chr11-66566127-C-T is described in ClinVar as Benign. ClinVar VariationId is 259172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.259 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003793.4. 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
	CTSF	NM_003793.4	MANE Select	c.762G>A	p.Arg254Arg	synonymous	Exon 6 of 13	NP_003784.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CTSF	ENST00000310325.10	TSL:1 MANE Select	c.762G>A	p.Arg254Arg	synonymous	Exon 6 of 13	ENSP00000310832.5
CTSF	ENST00000679347.1		c.762G>A	p.Arg254Arg	synonymous	Exon 6 of 13	ENSP00000503676.1
CTSF	ENST00000677005.1		c.762G>A	p.Arg254Arg	synonymous	Exon 6 of 13	ENSP00000503238.1

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92469

AN:

151906

Hom.:

29648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.823

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.527

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.635

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.580

GnomAD2 exomes

AF:

0.522

AC:

131149

AN:

251412

AF XY:

0.519

show subpopulations

Gnomad AFR exome

AF:

0.826

Gnomad AMR exome

AF:

0.328

Gnomad ASJ exome

AF:

0.545

Gnomad EAS exome

AF:

0.548

Gnomad FIN exome

AF:

0.634

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.537

AC:

784743

AN:

1461836

Hom.:

214603

Cov.:

AF XY:

0.534

AC XY:

388105

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.839

AC:

28073

AN:

33480

American (AMR)

AF:

0.342

AC:

15279

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

14036

AN:

26136

East Asian (EAS)

AF:

0.511

AC:

20304

AN:

39700

South Asian (SAS)

AF:

0.402

AC:

34644

AN:

86258

European-Finnish (FIN)

AF:

0.631

AC:

33690

AN:

53384

Middle Eastern (MID)

AF:

0.516

AC:

2979

AN:

5768

European-Non Finnish (NFE)

AF:

0.542

AC:

603041

AN:

1111996

Other (OTH)

AF:

0.541

AC:

32697

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

23851

47702

71553

95404

119255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17064

34128

51192

68256

85320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.609

AC:

92575

AN:

152024

Hom.:

29705

Cov.:

AF XY:

0.605

AC XY:

44931

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.824

AC:

34158

AN:

41460

American (AMR)

AF:

0.446

AC:

6818

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.527

AC:

1829

AN:

3468

East Asian (EAS)

AF:

0.532

AC:

2751

AN:

5168

South Asian (SAS)

AF:

0.395

AC:

1901

AN:

4812

European-Finnish (FIN)

AF:

0.635

AC:

6706

AN:

10564

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36648

AN:

67954

Other (OTH)

AF:

0.575

AC:

1213

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1751

3501

5252

7002

8753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.572

Hom.:

13053

Bravo

AF:

0.606

Asia WGS

AF:

0.491

AC:

1708

AN:

3478

EpiCase

AF:

0.541

EpiControl

AF:

0.540

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neuronal ceroid lipofuscinosis 13 (4)

not provided (4)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.6

(source)

DANN

Benign

0.54

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over