rs1369324

Positions:

• chr15-78947377-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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]

ACMG classification

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
CTSH	ENST00000528741.6	c.-24+2091T>C		intron_variant		5
CTSH	ENST00000677011.1	c.-211+2091T>C		intron_variant
CTSH	ENST00000530929.5	n.34+2091T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76474 AN: 151900 Hom.: 23484 Cov.: 31

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

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

Other links and lift over

dbSNP: rs1369324; hg19: chr15-79239719;