12-4574300-A-G

Position:

• chr12-4574300-A-G

Variant summary

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

The NM_001394779.1(DYRK4):​c.132+6252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,028 control chromosomes in the GnomAD database, including 46,620 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 0.78 (46620 hom., cov: 28)
• Consequence: DYRK4 NM_001394779.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

Genes affected

DYRK4 (HGNC:3095): (dual specificity tyrosine phosphorylation regulated kinase 4) This gene encodes an enzyme that belongs to a conserved family of serine/threonine protein kinases. Members of this dual specificity kinase family are thought to function in the regulation of cell differentiation and proliferation, survival, and in development. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Aug 2013]

DYRK4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYRK4	NM_001394779.1	c.132+6252A>G		intron_variant		ENST00000543431.6	NP_001381708.1
DYRK4	NM_001371301.2	c.132+6252A>G		intron_variant			NP_001358230.1
DYRK4	NM_001394780.1	c.114+944A>G		intron_variant			NP_001381709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYRK4	ENST00000543431.6	c.132+6252A>G		intron_variant		5	NM_001394779.1	ENSP00000439697.2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118106 AN: 150918 Hom.: 46582 Cov.: 28

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.783 AC: 118191 AN: 151028 Hom.: 46620 Cov.: 28 AF XY: 0.777 AC XY: 57212 AN XY: 73630

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.773

Alfa AF: 0.811 Hom.: 52211

Bravo AF: 0.788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10774241; hg19: chr12-4683466;