Variant chr8-29340104-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 NM_001394.7(DUSP4):c.573C>T(p.His191His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,571,422 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 15 hom. )

Consequence

DUSP4
NM_001394.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.797

Variant links:

Genes affected

DUSP4 (HGNC:3070): (dual specificity phosphatase 4) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported. [provided by RefSeq, Jul 2008]

DUSP4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 8-29340104-G-A is Benign according to our data. Variant chr8-29340104-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658512.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.797 with no splicing effect.

BS2

High AC in GnomAd4 at 304 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP4	NM_001394.7 linkuse as main transcript	c.573C>T	p.His191His	synonymous_variant	2/4	ENST00000240100.7	NP_001385.1	Q13115-1
DUSP4	NM_057158.4 linkuse as main transcript	c.300C>T	p.His100His	synonymous_variant	3/5		NP_476499.1	Q13115-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP4	ENST00000240100.7 linkuse as main transcript	c.573C>T	p.His191His	synonymous_variant	2/4	1	NM_001394.7	ENSP00000240100.2		Q13115-1
DUSP4	ENST00000240101.2 linkuse as main transcript	c.300C>T	p.His100His	synonymous_variant	3/5	1		ENSP00000240101.2		Q13115-2

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

304

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00304

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00201

AC:

368

AN:

183270

Hom.:

AF XY:

0.00195

AC XY:

191

AN XY:

97722

show subpopulations

Gnomad AFR exome

AF:

0.000574

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00136

Gnomad EAS exome

AF:

0.00180

Gnomad SAS exome

AF:

0.00178

Gnomad FIN exome

AF:

0.0000577

Gnomad NFE exome

AF:

0.00320

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00320

AC:

4547

AN:

1419136

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2191

AN XY:

701610

show subpopulations

Gnomad4 AFR exome

AF:

0.000460

Gnomad4 AMR exome

AF:

0.000983

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00375

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.0000791

Gnomad4 NFE exome

AF:

0.00366

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00200

AC:

304

AN:

152286

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00304

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00205

Hom.:

Bravo

AF:

0.00210

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

DUSP4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.12

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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