22-30664995-A-G

Position:

• chr22-30664995-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000334679.4(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 ENST00000334679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

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]

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DUSP18	NM_152511.5	c.-77-915T>C		intron_variant		ENST00000334679.4	NP_689724.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP18	ENST00000334679.4	c.-77-915T>C		intron_variant		1	NM_152511.5	ENSP00000333917	P1
	ENST00000673554.1	n.35A>G		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112633 AN: 152052 Hom.: 43887 Cov.: 34

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.: 0 AF XY: 0.825 AC XY: 226 AN XY: 274

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.853

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.909

Gnomad4 FIN exome AF: 0.944

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.741 AC: 112689 AN: 152170 Hom.: 43905 Cov.: 34 AF XY: 0.745 AC XY: 55471 AN XY: 74408

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.770

Alfa AF: 0.822 Hom.: 66294

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
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs5753268; hg19: chr22-31060982;