15-78947377-A-G

Variant summary

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

The ENST00000528741.6(CTSH):​c.-24+2091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,018 control chromosomes in the GnomAD database, including 23,492 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 0.50 ( 23492 hom., cov: 31)

Consequence

CTSH
ENST00000528741.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64
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]

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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=-1.0).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTSHENST00000528741.6 linkuse as main transcriptc.-24+2091T>C intron_variant 5
CTSHENST00000677011.1 linkuse as main transcriptc.-211+2091T>C intron_variant
CTSHENST00000530929.5 linkuse as main transcriptn.34+2091T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.503
AC:
76474
AN:
151900
Hom.:
23484
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.180
Gnomad AMI
AF:
0.689
Gnomad AMR
AF:
0.479
Gnomad ASJ
AF:
0.682
Gnomad EAS
AF:
0.104
Gnomad SAS
AF:
0.588
Gnomad FIN
AF:
0.631
Gnomad MID
AF:
0.621
Gnomad NFE
AF:
0.697
Gnomad OTH
AF:
0.527
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.503
AC:
76503
AN:
152018
Hom.:
23492
Cov.:
31
AF XY:
0.500
AC XY:
37159
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.180
Gnomad4 AMR
AF:
0.478
Gnomad4 ASJ
AF:
0.682
Gnomad4 EAS
AF:
0.104
Gnomad4 SAS
AF:
0.591
Gnomad4 FIN
AF:
0.631
Gnomad4 NFE
AF:
0.697
Gnomad4 OTH
AF:
0.531
Alfa
AF:
0.569
Hom.:
2634
Bravo
AF:
0.475
Asia WGS
AF:
0.359
AC:
1249
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.26
DANN
Benign
0.56

Splicing

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.

Other links and lift over

dbSNP: rs1369324; hg19: chr15-79239719; API