Variant 3-49284004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000265560.9(USP4):c.2523C>T(p.Val841=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,614,210 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 4 hom. )

Consequence

USP4
ENST00000265560.9 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

USP4 (HGNC:12627): (ubiquitin specific peptidase 4) The protein encoded by this gene is a protease that deubiquitinates target proteins such as ADORA2A and TRIM21. The encoded protein shuttles between the nucleus and cytoplasm and is involved in maintaining operational fidelity in the endoplasmic reticulum. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

USP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-49284004-G-A is Benign according to our data. Variant chr3-49284004-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 726623.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.39 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP4	NM_003363.4 linkuse as main transcript	c.2523C>T	p.Val841=	synonymous_variant	19/22	ENST00000265560.9	NP_003354.2
USP4	NM_199443.3 linkuse as main transcript	c.2382C>T	p.Val794=	synonymous_variant	18/21		NP_955475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP4	ENST00000265560.9 linkuse as main transcript	c.2523C>T	p.Val841=	synonymous_variant	19/22	1	NM_003363.4	ENSP00000265560	A1	Q13107-1
USP4	ENST00000351842.8 linkuse as main transcript	c.2382C>T	p.Val794=	synonymous_variant	18/21	1		ENSP00000341028	P4	Q13107-2
USP4	ENST00000431357.1 linkuse as main transcript	c.1740C>T	p.Val580=	synonymous_variant	13/15	5		ENSP00000399079
USP4	ENST00000485450.5 linkuse as main transcript	n.3037C>T		non_coding_transcript_exon_variant	13/16	2

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000354

AC:

AN:

251422

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000199

AC:

291

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

178

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00168

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.0000710

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000381

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000408

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.11

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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