rs4861387

Positions:

• chr4-41266448-G-A

Variant summary

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

The ENST00000284440.9(UCHL1):​c.586-1539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,884 control chromosomes in the GnomAD database, including 3,707 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 0.21 (3707 hom., cov: 31)
• Consequence: UCHL1 ENST00000284440.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

Genes affected

UCHL1 (HGNC:12513): (ubiquitin C-terminal hydrolase L1) The protein encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCHL1	NM_004181.5	c.586-1539G>A		intron_variant		ENST00000284440.9	NP_004172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCHL1	ENST00000284440.9	c.586-1539G>A		intron_variant		1	NM_004181.5	ENSP00000284440	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32588 AN: 151766 Hom.: 3704 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.215 AC: 32611 AN: 151884 Hom.: 3707 Cov.: 31 AF XY: 0.209 AC XY: 15535 AN XY: 74228

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0931

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.224

Alfa AF: 0.218 Hom.: 1650

Bravo AF: 0.218

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.58

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: rs4861387; hg19: chr4-41268465;