Genetic Variant DUSP18:c.-77-915T>C (chr22-30664995-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152511.5(DUSP18):c.-77-915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,614 control chromosomes in the GnomAD database, including 44,057 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 0.74 ( 43905 hom., cov: 34)

Exomes 𝑓: 0.82 ( 152 hom. )

Consequence

DUSP18
NM_152511.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.811

Publications

11 publications found

Variant links:

Genes affected

DUSP18 (HGNC:18484): (dual specificity phosphatase 18) Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. They have been implicated as major modulators of critical signaling pathways. DUSP18 contains the consensus DUSP C-terminal catalytic domain but lacks the N-terminal CH2 domain found in the MKP (mitogen-activated protein kinase phosphatase) class of DUSPs (see MIM 600714) (summary by Patterson et al., 2009 [PubMed 19228121]).[supplied by OMIM, Dec 2009]

DUSP18 links:

SLC35E4 (HGNC:17058): (solute carrier family 35 member E4) Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

SLC35E4 links:

ENSG00000288153 (HGNC:):

ENSG00000288153 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP18	NM_152511.5 link	c.-77-915T>C		intron_variant	Intron 1 of 1	ENST00000334679.4	NP_689724.3	Q8NEJ0A0A024R1L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP18	ENST00000334679.4 link	c.-77-915T>C		intron_variant	Intron 1 of 1	1	NM_152511.5	ENSP00000333917.3		Q8NEJ0

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112633

AN:

152052

Hom.:

43887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.881

Gnomad AMR

AF:

0.841

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.877

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.846

Gnomad OTH

AF:

0.767

GnomAD4 exome

AF:

0.824

AC:

366

AN:

444

Hom.:

152

Cov.:

AF XY:

0.825

AC XY:

226

AN XY:

274

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.853

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.909

AC:

AN:

European-Finnish (FIN)

AF:

0.944

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.815

AC:

269

AN:

330

Other (OTH)

AF:

0.864

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.741

AC:

112689

AN:

152170

Hom.:

43905

Cov.:

AF XY:

0.745

AC XY:

55471

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.464

AC:

19248

AN:

41480

American (AMR)

AF:

0.841

AC:

12869

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

2919

AN:

3470

East Asian (EAS)

AF:

0.877

AC:

4525

AN:

5160

South Asian (SAS)

AF:

0.871

AC:

4209

AN:

4830

European-Finnish (FIN)

AF:

0.825

AC:

8750

AN:

10606

Middle Eastern (MID)

AF:

0.810

AC:

238

AN:

294

European-Non Finnish (NFE)

AF:

0.846

AC:

57502

AN:

68004

Other (OTH)

AF:

0.770

AC:

1627

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1315

2630

3945

5260

6575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.812

Hom.:

91355

Bravo

AF:

0.730

Asia WGS

AF:

0.821

AC:

2851

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

(source)

DANN

Benign

0.59

PhyloP100

-0.81

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