rs11780602

Positions:

• chr8-29337930-A-G
• chr8-29337930-A-T

Variant summary

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

The NM_001394.7(DUSP4):​c.799+352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,936 control chromosomes in the GnomAD database, including 8,734 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 0.33 (8734 hom., cov: 31)
• Consequence: DUSP4 NM_001394.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP4	NM_001394.7	c.799+352T>C		intron_variant		ENST00000240100.7	NP_001385.1
DUSP4	NM_057158.4	c.526+352T>C		intron_variant			NP_476499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP4	ENST00000240100.7	c.799+352T>C		intron_variant		1	NM_001394.7	ENSP00000240100.2
DUSP4	ENST00000240101.2	c.526+352T>C		intron_variant		1		ENSP00000240101.2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50539 AN: 151818 Hom.: 8699 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.318

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.333 AC: 50627 AN: 151936 Hom.: 8734 Cov.: 31 AF XY: 0.335 AC XY: 24887 AN XY: 74276

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.315

Alfa AF: 0.315 Hom.: 958

Bravo AF: 0.339

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.35

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: rs11780602; hg19: chr8-29195447;