rs1369324

Variant names:

• chr15-78947377-A-G
• rs1369324
• ENST00000528741.6:c.-24+2091T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000528741.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSH	ENST00000528741.6	TSL:5	c.-24+2091T>C		intron	N/A	ENSP00000435329.2
	CTSH	ENST00000677011.1		c.-211+2091T>C		intron	N/A	ENSP00000504778.1
	CTSH	ENST00000530929.5	TSL:3	n.34+2091T>C		intron	N/A

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

African (AFR) AF: 0.180 AC: 7475 AN: 41478

American (AMR) AF: 0.478 AC: 7301 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2367 AN: 3472

East Asian (EAS) AF: 0.104 AC: 538 AN: 5160

South Asian (SAS) AF: 0.591 AC: 2848 AN: 4818

European-Finnish (FIN) AF: 0.631 AC: 6662 AN: 10566

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.697 AC: 47385 AN: 67944

Other (OTH) AF: 0.531 AC: 1122 AN: 2114

Alfa AF: 0.618 Hom.: 26498

Bravo AF: 0.475

Asia WGS AF: 0.359 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.56
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1369324; hg19: chr15-79239719;