rs4878127

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412179.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSL3P	ENST00000412179.5	TSL:6	n.-149T>C		upstream_gene	N/A

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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.125 AC: 6 AN: 48

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 20

European-Finnish (FIN) AF: 0.00605 AC: 3 AN: 496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00231 AC: 1 AN: 432

Other (OTH) AF: 0.00 AC: 0 AN: 18

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

African (AFR) AF: 0.0661 AC: 2745 AN: 41552

American (AMR) AF: 0.0688 AC: 1053 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0356 AC: 172 AN: 4828

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00276 AC: 188 AN: 68030

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0181 Hom.: 11

Bravo AF: 0.0341

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.49
PhyloP100		0.088

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4878127;

hg19: chr9-90387219;