Variant rs12148472 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.123+4A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,596,550 control chromosomes in the GnomAD database, including 13,660 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 0.14 ( 1531 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12129 hom. )

Consequence

CTSH
NM_004390.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.2561

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

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=-0.49).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CTSH	NM_004390.5 linkuse as main transcript	c.123+4A>G	splice_donor_region_variant, intron_variant	ENST00000220166.10
CTSH	NM_001319137.2 linkuse as main transcript	c.-953+4A>G	splice_donor_region_variant, intron_variant
CTSH	NM_001411095.1 linkuse as main transcript	c.9+4A>G	splice_donor_region_variant, intron_variant
CTSH	XM_017021951.2 linkuse as main transcript	c.-70+4A>G	splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSH	ENST00000220166.10 linkuse as main transcript	c.123+4A>G		splice_donor_region_variant, intron_variant		1	NM_004390.5	P1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20763

AN:

151852

Hom.:

1531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0916

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0619

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.121

AC:

28483

AN:

235996

Hom.:

1835

AF XY:

0.123

AC XY:

15613

AN XY:

127386

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.0771

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.0637

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.126

AC:

182655

AN:

1444580

Hom.:

12129

Cov.:

AF XY:

0.128

AC XY:

91581

AN XY:

718284

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.0768

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.0622

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.137

AC:

20779

AN:

151970

Hom.:

1531

Cov.:

AF XY:

0.135

AC XY:

10058

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.0916

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.0616

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.124

Hom.:

2084

Bravo

AF:

0.133

Asia WGS

AF:

0.111

AC:

386

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.26

dbscSNV1_RF

Benign

0.21

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