chr4-41256671-A-G

Variant names:

• chr4-41256671-A-G
• rs73809700
• ENST00000514924.5:c.-118A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000514924.5(UCHL1):​c.-118A>G 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 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 ENST00000514924.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.30
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1246763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514924.5. 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
	UCHL1-DT	NR_102709.1		n.57T>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCHL1	ENST00000514924.5	TSL:3	c.-118A>G		5_prime_UTR	Exon 2 of 5	ENSP00000426634.1	D6RF53
	UCHL1-DT	ENST00000507190.1	TSL:4	n.57T>C		non_coding_transcript_exon	Exon 1 of 3
	UCHL1-DT	ENST00000510073.1	TSL:3	n.51T>C		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.0467 AC: 539 AN: 11552

American (AMR) AF: 0.131 AC: 2220 AN: 16980

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 2605 AN: 12306

East Asian (EAS) AF: 0.000475 AC: 13 AN: 27362

South Asian (SAS) AF: 0.0679 AC: 2737 AN: 40316

European-Finnish (FIN) AF: 0.168 AC: 4296 AN: 25496

Middle Eastern (MID) AF: 0.181 AC: 316 AN: 1746

European-Non Finnish (NFE) AF: 0.217 AC: 51385 AN: 237056

Other (OTH) AF: 0.178 AC: 4147 AN: 23262

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

African (AFR) AF: 0.0456 AC: 1896 AN: 41542

American (AMR) AF: 0.137 AC: 2097 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5174

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4826

European-Finnish (FIN) AF: 0.166 AC: 1757 AN: 10584

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14592 AN: 67984

Other (OTH) AF: 0.174 AC: 369 AN: 2116

Alfa AF: 0.165 Hom.: 319

Bravo AF: 0.143

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		2.3
PromoterAI		-0.0048	Neutral

Splicing

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

Other links and lift over

dbSNP: rs73809700; hg19: chr4-41258688;