4-41256671-A-G

Variant summary

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

The NR_102709.1(UCHL1-DT):n.57T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 548,264 control chromosomes in the GnomAD database, including 9,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2154 hom., cov: 33)
  • Exomes 𝑓: 0.17 (6908 hom.)
• Consequence: UCHL1-DT NR_102709.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.30

Genes affected

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

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 4-41256671-A-G is Benign according to our data. Variant chr4-41256671-A-G is described in ClinVar as [Benign]. Clinvar id is 1246763.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	n.57T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCHL1-DT	ENST00000507190.1	n.57T>C		non_coding_transcript_exon_variant	1/3	4
UCHL1	ENST00000514924.5	c.-118A>G		5_prime_UTR_variant	2/5	3
UCHL1-DT	ENST00000510073.1	n.51T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22128 AN: 152070 Hom.: 2154 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: 0.000964

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.172 AC: 68258 AN: 396076 Hom.: 6908 Cov.: 2 AF XY: 0.167 AC XY: 34570 AN XY: 206668

Gnomad4 AFR exome AF: 0.0467

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.000475

Gnomad4 SAS exome AF: 0.0679

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.145 AC: 22132 AN: 152188 Hom.: 2154 Cov.: 33 AF XY: 0.140 AC XY: 10429 AN XY: 74394

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.174

Alfa AF: 0.165 Hom.: 319

Bravo AF: 0.143

Asia WGS AF: 0.0420 AC: 144 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	-0.75
Cadd	Benign	13
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73809700; hg19: chr4-41258688;