NM_001909.5:c.828-17G>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.828-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 1,604,836 control chromosomes in the GnomAD database, including 4,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 272 hom., cov: 33)

Exomes 𝑓: 0.070 ( 3948 hom. )

Consequence

CTSD
NM_001909.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.09

Publications

7 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 (MetaRNN=0.0028076768).

BP6

Variant 11-1754155-C-T is Benign according to our data. Variant chr11-1754155-C-T is described in ClinVar as Benign. ClinVar VariationId is 258490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSD	NM_001909.5 link	c.828-17G>A		intron_variant	Intron 6 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.828-17G>A		intron_variant	Intron 6 of 8	1	NM_001909.5	ENSP00000236671.2		P07339
ENSG00000250644	ENST00000636615.1 link	c.828-17G>A		intron_variant	Intron 6 of 9	5		ENSP00000490014.1		A0A1B0GU92

Frequencies

GnomAD3 genomes

AF:

0.0550

AC:

8372

AN:

152104

Hom.:

271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0614

Gnomad ASJ

AF:

0.0902

Gnomad EAS

AF:

0.0291

Gnomad SAS

AF:

0.0886

Gnomad FIN

AF:

0.0422

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0716

Gnomad OTH

AF:

0.0708

GnomAD2 exomes

AF:

0.0636

AC:

14967

AN:

235162

AF XY:

0.0674

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.0422

Gnomad ASJ exome

AF:

0.0957

Gnomad EAS exome

AF:

0.0340

Gnomad FIN exome

AF:

0.0462

Gnomad NFE exome

AF:

0.0714

Gnomad OTH exome

AF:

0.0788

GnomAD4 exome

AF:

0.0705

AC:

102338

AN:

1452614

Hom.:

3948

Cov.:

AF XY:

0.0714

AC XY:

51633

AN XY:

722702

show subpopulations

African (AFR)

AF:

0.0233

AC:

779

AN:

33404

American (AMR)

AF:

0.0436

AC:

1938

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.0890

AC:

2319

AN:

26060

East Asian (EAS)

AF:

0.0257

AC:

1015

AN:

39560

South Asian (SAS)

AF:

0.0936

AC:

8028

AN:

85810

European-Finnish (FIN)

AF:

0.0464

AC:

2171

AN:

46826

Middle Eastern (MID)

AF:

0.112

AC:

640

AN:

5724

European-Non Finnish (NFE)

AF:

0.0730

AC:

81062

AN:

1110610

Other (OTH)

AF:

0.0729

AC:

4386

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

5129

10258

15388

20517

25646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3018

6036

9054

12072

15090

<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:

0.0550

AC:

8367

AN:

152222

Hom.:

272

Cov.:

AF XY:

0.0539

AC XY:

4007

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0245

AC:

1019

AN:

41564

American (AMR)

AF:

0.0613

AC:

938

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0902

AC:

313

AN:

3470

East Asian (EAS)

AF:

0.0288

AC:

148

AN:

5142

South Asian (SAS)

AF:

0.0883

AC:

426

AN:

4826

European-Finnish (FIN)

AF:

0.0422

AC:

448

AN:

10622

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0716

AC:

4870

AN:

67976

Other (OTH)

AF:

0.0720

AC:

152

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

392

784

1176

1568

1960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0708

Hom.:

131

Bravo

AF:

0.0540

TwinsUK

AF:

0.0693

AC:

257

ALSPAC

AF:

0.0729

AC:

281

ESP6500AA

AF:

0.0248

AC:

109

ESP6500EA

AF:

0.0693

AC:

596

ExAC

AF:

0.0614

AC:

7416

Asia WGS

AF:

0.0790

AC:

272

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 15, 2015

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 10

Benign:2

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neuronal ceroid lipofuscinosis

Benign:1

Feb 04, 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

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.017

(source)

DANN

Benign

0.87

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

PhyloP100

-3.1

PROVEAN

Benign

0.0

REVEL

Benign

0.13

Sift

Uncertain

0.0050

Sift4G

Benign

0.19

ClinPred

0.0022

GERP RS

-5.6

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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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