Variant rs11638844 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004390.5(CTSH):c.92-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,584,466 control chromosomes in the GnomAD database, including 337,609 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 24396 hom., cov: 32)

Exomes 𝑓: 0.66 ( 313213 hom. )

Consequence

CTSH
NM_004390.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003227

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.199

Variant links:

Genes affected

CTSH (HGNC:2535): (cathepsin H) The protein encoded by this gene is a lysosomal cysteine proteinase important in the overall degradation of lysosomal proteins. It is composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. The encoded protein, which belongs to the peptidase C1 protein family, can act both as an aminopeptidase and as an endopeptidase. Increased expression of this gene has been correlated with malignant progression of prostate tumors. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

CTSH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CTSH	NM_004390.5 linkuse as main transcript	c.92-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000220166.10	NP_004381.2
CTSH	NM_001319137.2 linkuse as main transcript	c.-984-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001306066.1
CTSH	NM_001411095.1 linkuse as main transcript	c.-23-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001398024.1
CTSH	XM_017021951.2 linkuse as main transcript	c.-101-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_016877440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSH	ENST00000220166.10 linkuse as main transcript	c.92-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004390.5	ENSP00000220166	P1

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81633

AN:

151620

Hom.:

24380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.710

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.543

GnomAD3 exomes

AF:

0.603

AC:

139403

AN:

231282

Hom.:

43517

AF XY:

0.613

AC XY:

76679

AN XY:

125110

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.569

Gnomad ASJ exome

AF:

0.668

Gnomad EAS exome

AF:

0.468

Gnomad SAS exome

AF:

0.632

Gnomad FIN exome

AF:

0.618

Gnomad NFE exome

AF:

0.668

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.656

AC:

939748

AN:

1432728

Hom.:

313213

Cov.:

AF XY:

0.657

AC XY:

467952

AN XY:

712566

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.574

Gnomad4 ASJ exome

AF:

0.673

Gnomad4 EAS exome

AF:

0.450

Gnomad4 SAS exome

AF:

0.643

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.634

GnomAD4 genome

AF:

0.538

AC:

81683

AN:

151738

Hom.:

24396

Cov.:

AF XY:

0.538

AC XY:

39912

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.664

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.630

Gnomad4 FIN

AF:

0.610

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.617

Hom.:

19630

Bravo

AF:

0.524

Asia WGS

AF:

0.542

AC:

1884

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.55

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over