NM_004390.5:c.92-2755A>G

Variant names:

• chr15-78941926-T-C
• rs2870085
• NM_004390.5:c.92-2755A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004390.5(CTSH):​c.92-2755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,058 control chromosomes in the GnomAD database, including 22,837 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 0.51 (22837 hom., cov: 33)
• Consequence: CTSH NM_004390.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 20 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSH	NM_004390.5	c.92-2755A>G		intron_variant	Intron 1 of 11	ENST00000220166.10	NP_004381.2
CTSH	NM_001411095.1	c.-23-2755A>G		intron_variant	Intron 1 of 11		NP_001398024.1
CTSH	NM_001319137.2	c.-984-2755A>G		intron_variant	Intron 1 of 12		NP_001306066.1
CTSH	XM_017021951.2	c.-101-2755A>G		intron_variant	Intron 1 of 12		XP_016877440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSH	ENST00000220166.10	c.92-2755A>G		intron_variant	Intron 1 of 11	1	NM_004390.5	ENSP00000220166.6

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77152 AN: 151938 Hom.: 22828 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77184 AN: 152058 Hom.: 22837 Cov.: 33 AF XY: 0.505 AC XY: 37534 AN XY: 74326

African (AFR) AF: 0.236 AC: 9785 AN: 41470

American (AMR) AF: 0.469 AC: 7164 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2299 AN: 3462

East Asian (EAS) AF: 0.106 AC: 550 AN: 5180

South Asian (SAS) AF: 0.611 AC: 2945 AN: 4822

European-Finnish (FIN) AF: 0.615 AC: 6494 AN: 10556

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46057 AN: 67974

Other (OTH) AF: 0.520 AC: 1099 AN: 2114

Alfa AF: 0.617 Hom.: 102744

Bravo AF: 0.481

Asia WGS AF: 0.377 AC: 1313 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	1.8
DANN	Benign	0.66
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2870085; hg19: chr15-79234268;