15-78921873-C-T

Position:

• chr15-78921873-C-T

Variant summary

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

The NM_004390.5(CTSH):​c.*257G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 512,182 control chromosomes in the GnomAD database, including 15,307 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 0.22 (3996 hom., cov: 32)
  • Exomes 𝑓: 0.24 (11311 hom.)
• Consequence: CTSH NM_004390.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

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]

CTSH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSH	NM_004390.5	c.*257G>A		3_prime_UTR_variant	12/12	ENST00000220166.10	NP_004381.2
CTSH	NM_001411095.1	c.*257G>A		3_prime_UTR_variant	12/12		NP_001398024.1
CTSH	NM_001319137.2	c.*257G>A		3_prime_UTR_variant	13/13		NP_001306066.1
CTSH	XM_017021951.2	c.*257G>A		3_prime_UTR_variant	13/13		XP_016877440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSH	ENST00000220166	c.*257G>A		3_prime_UTR_variant	12/12	1	NM_004390.5	ENSP00000220166.6

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32754 AN: 152066 Hom.: 3995 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.237 AC: 85399 AN: 359998 Hom.: 11311 Cov.: 0 AF XY: 0.236 AC XY: 44205 AN XY: 186986

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.0516

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.215 AC: 32759 AN: 152184 Hom.: 3996 Cov.: 32 AF XY: 0.217 AC XY: 16124 AN XY: 74394

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.0388

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.208

Alfa AF: 0.223 Hom.: 1802

Bravo AF: 0.198

Asia WGS AF: 0.122 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3129; hg19: chr15-79214215;