Genetic Variant DUSP1:p.Ile200Ile (chr5-172769708-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004417.4(DUSP1):c.600C>A(p.Ile200Ile) variant causes a synonymous change. The variant allele was found at a frequency of 0.937 in 1,614,160 control chromosomes in the GnomAD database, including 714,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.86 ( 57746 hom., cov: 34)

Exomes 𝑓: 0.95 ( 656745 hom. )

Consequence

DUSP1
NM_004417.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.81

Publications

29 publications found

Variant links:

Genes affected

DUSP1 (HGNC:3064): (dual specificity phosphatase 1) The protein encoded by this gene is a phosphatase with dual specificity for tyrosine and threonine. The encoded protein can dephosphorylate MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes. This protein appears to play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. Finally, the encoded protein can make some solid tumors resistant to both chemotherapy and radiotherapy, making it a target for cancer therapy. [provided by RefSeq, Aug 2017]

DUSP1 links:

ENSG00000253736 (HGNC:):

ENSG00000253736 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP1	NM_004417.4 link	c.600C>A	p.Ile200Ile	synonymous_variant	Exon 3 of 4	ENST00000239223.4	NP_004408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP1	ENST00000239223.4 link	c.600C>A	p.Ile200Ile	synonymous_variant	Exon 3 of 4	1	NM_004417.4	ENSP00000239223.3
ENSG00000253736	ENST00000523005.1 link	n.69+6660G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.856

AC:

130227

AN:

152154

Hom.:

57720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.988

Gnomad AMR

AF:

0.937

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.983

Gnomad FIN

AF:

0.952

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.953

Gnomad OTH

AF:

0.883

GnomAD2 exomes

AF:

0.938

AC:

235831

AN:

251492

AF XY:

0.945

show subpopulations

Gnomad AFR exome

AF:

0.589

Gnomad AMR exome

AF:

0.962

Gnomad ASJ exome

AF:

0.976

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.951

Gnomad NFE exome

AF:

0.952

Gnomad OTH exome

AF:

0.949

GnomAD4 exome

AF:

0.946

AC:

1382935

AN:

1461888

Hom.:

656745

Cov.:

AF XY:

0.948

AC XY:

689587

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.574

AC:

19233

AN:

33480

American (AMR)

AF:

0.959

AC:

42898

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.976

AC:

25496

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39697

AN:

39700

South Asian (SAS)

AF:

0.980

AC:

84534

AN:

86258

European-Finnish (FIN)

AF:

0.951

AC:

50829

AN:

53420

Middle Eastern (MID)

AF:

0.942

AC:

5431

AN:

5766

European-Non Finnish (NFE)

AF:

0.952

AC:

1058150

AN:

1112010

Other (OTH)

AF:

0.938

AC:

56667

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

4408

8816

13224

17632

22040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21564

43128

64692

86256

107820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.856

AC:

130296

AN:

152272

Hom.:

57746

Cov.:

AF XY:

0.860

AC XY:

63995

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.594

AC:

24644

AN:

41510

American (AMR)

AF:

0.937

AC:

14342

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.973

AC:

3375

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5184

AN:

5186

South Asian (SAS)

AF:

0.984

AC:

4753

AN:

4832

European-Finnish (FIN)

AF:

0.952

AC:

10104

AN:

10618

Middle Eastern (MID)

AF:

0.908

AC:

267

AN:

294

European-Non Finnish (NFE)

AF:

0.953

AC:

64857

AN:

68032

Other (OTH)

AF:

0.884

AC:

1869

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

784

1567

2351

3134

3918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.918

Hom.:

88241

Bravo

AF:

0.842

Asia WGS

AF:

0.974

AC:

3387

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

5.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over