chr11-1759104-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001909.5(CTSD):c.353-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,576,698 control chromosomes in the GnomAD database, including 1,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 953 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 847 hom. )

Consequence

CTSD
NM_001909.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.135

Publications

1 publications found

Variant links:

Genes affected

CTSD (HGNC:2529): (cathepsin D) This gene encodes a member of the A1 family of peptidases. The encoded preproprotein is proteolytically processed to generate multiple protein products. These products include the cathepsin D light and heavy chains, which heterodimerize to form the mature enzyme. This enzyme exhibits pepsin-like activity and plays a role in protein turnover and in the proteolytic activation of hormones and growth factors. Mutations in this gene play a causal role in neuronal ceroid lipofuscinosis-10 and may be involved in the pathogenesis of several other diseases, including breast cancer and possibly Alzheimer's disease. [provided by RefSeq, Nov 2015]

CTSD Gene-Disease associations (from GenCC):

neuronal ceroid lipofuscinosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuronal ceroid lipofuscinosis 10
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp

CTSD links:

ENSG00000250644 (HGNC:):

ENSG00000250644 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-1759104-G-A is Benign according to our data. Variant chr11-1759104-G-A is described in ClinVar as [Benign]. Clinvar id is 137054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSD	NM_001909.5 link	c.353-17C>T		intron_variant	Intron 3 of 8	ENST00000236671.7	NP_001900.1	P07339V9HWI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSD	ENST00000236671.7 link	c.353-17C>T		intron_variant	Intron 3 of 8	1	NM_001909.5	ENSP00000236671.2		P07339
ENSG00000250644	ENST00000636615.1 link	c.353-17C>T		intron_variant	Intron 3 of 9	5		ENSP00000490014.1		A0A1B0GU92

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

9391

AN:

152174

Hom.:

951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0211

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0425

GnomAD2 exomes

AF:

0.0156

AC:

3911

AN:

250584

AF XY:

0.0116

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.00919

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000558

Gnomad OTH exome

AF:

0.00654

GnomAD4 exome

AF:

0.00621

AC:

8844

AN:

1424406

Hom.:

847

Cov.:

AF XY:

0.00530

AC XY:

3769

AN XY:

710808

show subpopulations

African (AFR)

AF:

0.216

AC:

7100

AN:

32802

American (AMR)

AF:

0.0111

AC:

495

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.00

AC:

AN:

39470

South Asian (SAS)

AF:

0.000269

AC:

AN:

85502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00595

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.000357

AC:

385

AN:

1077950

Other (OTH)

AF:

0.0137

AC:

807

AN:

59116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

378

756

1133

1511

1889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0617

AC:

9399

AN:

152292

Hom.:

953

Cov.:

AF XY:

0.0601

AC XY:

4473

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.215

AC:

8922

AN:

41536

American (AMR)

AF:

0.0210

AC:

322

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68022

Other (OTH)

AF:

0.0421

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

393

785

1178

1570

1963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.0699

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 06, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Apr 25, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Neuronal ceroid lipofuscinosis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.1

(source)

DANN

Benign

0.67

PhyloP100

-0.14

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

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

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chr11-1759104-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over