rs1428157464

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_001909.5(CTSD):c.933G>A(p.Leu311Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,670 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 1 hom. )

Consequence

CTSD
NM_001909.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.788

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.165).

BP6

Variant 11-1754033-C-T is Benign according to our data. Variant chr11-1754033-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 527760.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.788 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00000412 (6/1457670) while in subpopulation MID AF = 0.000695 (4/5754). AF 95% confidence interval is 0.000236. There are 1 homozygotes in GnomAdExome4. There are 3 alleles in the male GnomAdExome4 subpopulation. Median coverage is 38. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSD	NM_001909.5 link	c.933G>A	p.Leu311Leu	synonymous_variant	Exon 7 of 9	ENST00000236671.7	NP_001900.1	P07339V9HWI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSD	ENST00000236671.7 link	c.933G>A	p.Leu311Leu	synonymous_variant	Exon 7 of 9	1	NM_001909.5	ENSP00000236671.2		P07339
ENSG00000250644	ENST00000636615.1 link	c.933G>A	p.Leu311Leu	synonymous_variant	Exon 7 of 10	5		ENSP00000490014.1		A0A1B0GU92

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

243104

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000504

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1457670

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725114

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33412

American (AMR)

AF:

0.00

AC:

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39582

South Asian (SAS)

AF:

0.00

AC:

AN:

86014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51134

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110992

Other (OTH)

AF:

0.00

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neuronal ceroid lipofuscinosis

Benign:1

Jul 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.55

CADD

Benign

2.6

(source)

DANN

Benign

0.71

PhyloP100

0.79

PromoterAI

-0.0084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over