rs4878127

Variant names:

• chr9-87772304-T-C
• rs4878127
• ENST00000412179.5:n.-149T>C

Variant summary

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

The ENST00000412179.5(CTSL3P):​n.-149T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 153,342 control chromosomes in the GnomAD database, including 155 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 0.028 (154 hom., cov: 33)
  • Exomes 𝑓: 0.011 (1 hom.)
• Consequence: CTSL3P ENST00000412179.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

Genes affected

CTSL3P (HGNC:33132): (cathepsin L family member 3, pseudogene) Predicted to enable cysteine-type endopeptidase activity. Predicted to be involved in proteolysis involved in cellular protein catabolic process. Predicted to be active in extracellular space and lysosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSL3P	ENST00000412179.5	n.-149T>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4255 AN: 152196 Hom.: 151 Cov.: 33

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0107 AC: 11 AN: 1028 Hom.: 1 AF XY: 0.0152 AC XY: 9 AN XY: 594

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00605

Gnomad4 NFE exome AF: 0.00231

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0280 AC: 4269 AN: 152314 Hom.: 154 Cov.: 33 AF XY: 0.0290 AC XY: 2163 AN XY: 74484

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00276

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0159 Hom.: 8

Bravo AF: 0.0341

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4878127; hg19: chr9-90387219;