Variant 11-1761176-G-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_001909.5(CTSD):c.228+133C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 936,290 control chromosomes in the GnomAD database, including 3,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 560 hom., cov: 33)

Exomes 𝑓: 0.079 ( 2705 hom. )

Consequence

CTSD
NM_001909.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.59

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 links:

ENSG00000250644 (HGNC:):

ENSG00000250644 links:

PRADX (HGNC:40168): (PRC2 and DDX5 associated lncRNA)

PRADX 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=-0.91).

BP6

Variant 11-1761176-G-C is Benign according to our data. Variant chr11-1761176-G-C is described in ClinVar as [Benign]. Clinvar id is 1295669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSD	NM_001909.5 link	c.228+133C>G		intron_variant		ENST00000236671.7	NP_001900.1	P07339V9HWI3
PRADX	NR_182291.1 link	n.829G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSD	ENST00000236671.7 link	c.228+133C>G		intron_variant		1	NM_001909.5	ENSP00000236671.2		P07339
ENSG00000250644	ENST00000636615.1 link	c.228+133C>G		intron_variant		5		ENSP00000490014.1		A0A1B0GU92

Frequencies

GnomAD3 genomes

AF:

0.0832

AC:

12659

AN:

152098

Hom.:

555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0955

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.0287

Gnomad SAS

AF:

0.0921

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0847

Gnomad OTH

AF:

0.0913

GnomAD4 exome

AF:

0.0792

AC:

62115

AN:

784074

Hom.:

2705

Cov.:

AF XY:

0.0802

AC XY:

32752

AN XY:

408324

show subpopulations

Gnomad4 AFR exome

AF:

0.0977

Gnomad4 AMR exome

AF:

0.0527

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0233

Gnomad4 SAS exome

AF:

0.0965

Gnomad4 FIN exome

AF:

0.0507

Gnomad4 NFE exome

AF:

0.0825

Gnomad4 OTH exome

AF:

0.0856

GnomAD4 genome

AF:

0.0833

AC:

12672

AN:

152216

Hom.:

560

Cov.:

AF XY:

0.0806

AC XY:

6002

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0955

Gnomad4 AMR

AF:

0.0810

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.0286

Gnomad4 SAS

AF:

0.0917

Gnomad4 FIN

AF:

0.0461

Gnomad4 NFE

AF:

0.0847

Gnomad4 OTH

AF:

0.0932

Alfa

AF:

0.0310

Hom.:

Bravo

AF:

0.0853

Asia WGS

AF:

0.0890

AC:

309

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.14

DANN

Benign

0.34

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