Variant 11-66567837-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003793.4(CTSF):c.312+147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,359,172 control chromosomes in the GnomAD database, including 37,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 3911 hom., cov: 32)

Exomes 𝑓: 0.23 ( 33139 hom. )

Consequence

CTSF
NM_003793.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.632

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-66567837-T-C is Benign according to our data. Variant chr11-66567837-T-C is described in ClinVar as [Benign]. Clinvar id is 1271666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSF	NM_003793.4 link	c.312+147A>G		intron_variant		ENST00000310325.10	NP_003784.2	Q9UBX1
CTSF	XM_011545328.3 link	c.132+147A>G		intron_variant			XP_011543630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSF	ENST00000310325.10 link	c.312+147A>G		intron_variant		1	NM_003793.4	ENSP00000310832.5		Q9UBX1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34287

AN:

151988

Hom.:

3912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.230

AC:

277955

AN:

1207066

Hom.:

33139

Cov.:

AF XY:

0.228

AC XY:

135366

AN XY:

593636

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.225

AC:

34289

AN:

152106

Hom.:

3911

Cov.:

AF XY:

0.221

AC XY:

16439

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.244

Hom.:

3059

Bravo

AF:

0.229

Asia WGS

AF:

0.186

AC:

649

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

DANN

Benign

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over