Variant 4-41257096-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004181.5(UCHL1):c.34-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,613,794 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 36 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 37 hom. )

Consequence

UCHL1
NM_004181.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.641

Variant links:

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 links:

UCHL1 (HGNC:):

UCHL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 4-41257096-C-T is Benign according to our data. Variant chr4-41257096-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1742/152330) while in subpopulation AFR AF= 0.0382 (1588/41584). AF 95% confidence interval is 0.0366. There are 36 homozygotes in gnomad4. There are 807 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1742 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCHL1	NM_004181.5 linkuse as main transcript	c.34-19C>T		intron_variant		ENST00000284440.9	NP_004172.2	P09936V9HW74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCHL1	ENST00000284440.9 linkuse as main transcript	c.34-19C>T		intron_variant		1	NM_004181.5	ENSP00000284440.4		P09936

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1735

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00329

AC:

828

AN:

251314

Hom.:

AF XY:

0.00255

AC XY:

346

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0387

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00145

AC:

2120

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

995

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.00302

Gnomad4 ASJ exome

AF:

0.00283

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.00340

GnomAD4 genome

AF:

0.0114

AC:

1742

AN:

152330

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

807

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0382

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00693

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.8

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over