15-78943104-T-C

Position:

• chr15-78943104-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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/exons	MANE	Protein	UniProt
CTSH	NM_004390.5	c.91+1787A>G		intron_variant		ENST00000220166.10	NP_004381.2
CTSH	NM_001319137.2	c.-985+1787A>G		intron_variant			NP_001306066.1
CTSH	NM_001411095.1	c.-24+1674A>G		intron_variant			NP_001398024.1
CTSH	XM_017021951.2	c.-102+1787A>G		intron_variant			XP_016877440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSH	ENST00000220166.10	c.91+1787A>G		intron_variant		1	NM_004390.5	ENSP00000220166	P1

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

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.516

Alfa AF: 0.626 Hom.: 40966

Bravo AF: 0.475

Asia WGS AF: 0.373 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.84
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs3825932; hg19: chr15-79235446;