Variant 15-78932341-C-T 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.492+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,599,172 control chromosomes in the GnomAD database, including 22,570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 4383 hom., cov: 32)

Exomes 𝑓: 0.12 ( 18187 hom. )

Consequence

CTSH
NM_004390.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.190

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:

CTSH (HGNC:):

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CTSH	NM_004390.5 linkuse as main transcript	c.492+31G>A	intron_variant	ENST00000220166.10	NP_004381.2	P09668
CTSH	NM_001411095.1 linkuse as main transcript	c.378+31G>A	intron_variant		NP_001398024.1
CTSH	NM_001319137.2 linkuse as main transcript	c.-446+31G>A	intron_variant		NP_001306066.1
CTSH	XM_017021951.2 linkuse as main transcript	c.438+31G>A	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.492+31G>A		intron_variant		1	NM_004390.5	ENSP00000220166.6		P09668

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29872

AN:

152036

Hom.:

4374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.0932

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0834

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0966

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.178

AC:

44536

AN:

250006

Hom.:

7126

AF XY:

0.163

AC XY:

22066

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.0967

Gnomad EAS exome

AF:

0.646

Gnomad SAS exome

AF:

0.0890

Gnomad FIN exome

AF:

0.0865

Gnomad NFE exome

AF:

0.0972

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.122

AC:

177211

AN:

1447018

Hom.:

18187

Cov.:

AF XY:

0.120

AC XY:

86367

AN XY:

720782

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.0966

Gnomad4 EAS exome

AF:

0.612

Gnomad4 SAS exome

AF:

0.0918

Gnomad4 FIN exome

AF:

0.0872

Gnomad4 NFE exome

AF:

0.0951

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.197

AC:

29905

AN:

152154

Hom.:

4383

Cov.:

AF XY:

0.198

AC XY:

14765

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.245

Gnomad4 ASJ

AF:

0.0932

Gnomad4 EAS

AF:

0.628

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0834

Gnomad4 NFE

AF:

0.0966

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.122

Hom.:

1308

Bravo

AF:

0.220

Asia WGS

AF:

0.330

AC:

1149

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.6

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over