4-41256745-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000514924.5(UCHL1):c.-44G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 632,874 control chromosomes in the GnomAD database, including 10,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2145 hom., cov: 33)
  • Exomes 𝑓: 0.17 (8323 hom.)
• Consequence: UCHL1 ENST00000514924.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.90

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]

UCHL1-DT (HGNC:40600): (UCHL1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 4-41256745-G-A is Benign according to our data. Variant chr4-41256745-G-A is described in ClinVar as [Benign]. Clinvar id is 1283154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCHL1-DT	NR_102709.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCHL1	ENST00000514924.5	c.-44G>A		5_prime_UTR_variant	2/5	3
UCHL1-DT	ENST00000507190.1			upstream_gene_variant		4
UCHL1	ENST00000503431.5			upstream_gene_variant		3		P1
UCHL1-DT	ENST00000510073.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22099 AN: 152014 Hom.: 2145 Cov.: 33

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.172 AC: 82614 AN: 480742 Hom.: 8323 Cov.: 5 AF XY: 0.167 AC XY: 42559 AN XY: 254360

Gnomad4 AFR exome AF: 0.0459

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.000415

Gnomad4 SAS exome AF: 0.0671

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.145 AC: 22102 AN: 152132 Hom.: 2145 Cov.: 33 AF XY: 0.140 AC XY: 10409 AN XY: 74330

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0567

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.174

Alfa AF: 0.172 Hom.: 342

Bravo AF: 0.143

Asia WGS AF: 0.0410 AC: 142 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	17
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73809701; hg19: chr4-41258762;