NM_004390.5:c.91+1787A>G

Variant names:

• chr15-78943104-T-C
• rs3825932
• NM_004390.5:c.91+1787A>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.91+1787A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,994 control chromosomes in the GnomAD database, including 22,662 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 (22662 hom., cov: 30)
• Consequence: CTSH NM_004390.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 118 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004390.5. 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
	CTSH	NM_004390.5	MANE Select	c.91+1787A>G		intron	N/A	NP_004381.2
	CTSH	NM_001411095.1		c.-24+1674A>G		intron	N/A	NP_001398024.1
	CTSH	NM_001319137.2		c.-985+1787A>G		intron	N/A	NP_001306066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSH	ENST00000220166.10	TSL:1 MANE Select	c.91+1787A>G		intron	N/A	ENSP00000220166.6
	CTSH	ENST00000615999.5	TSL:1	c.91+1787A>G		intron	N/A	ENSP00000483303.2
	CTSH	ENST00000527715.6	TSL:1	n.139+1787A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76336 AN: 151876 Hom.: 22654 Cov.: 30

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.502 AC: 76365 AN: 151994 Hom.: 22662 Cov.: 30 AF XY: 0.500 AC XY: 37130 AN XY: 74286

African (AFR) AF: 0.218 AC: 9043 AN: 41462

American (AMR) AF: 0.467 AC: 7140 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3468

East Asian (EAS) AF: 0.106 AC: 549 AN: 5176

South Asian (SAS) AF: 0.612 AC: 2944 AN: 4810

European-Finnish (FIN) AF: 0.616 AC: 6498 AN: 10554

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46010 AN: 67932

Other (OTH) AF: 0.516 AC: 1088 AN: 2108

Alfa AF: 0.602 Hom.: 100126

Bravo AF: 0.475

Asia WGS AF: 0.373 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.84
DANN	Benign	0.88
PhyloP100		-1.4
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: rs3825932; hg19: chr15-79235446;