chr12-4574300-A-C

Variant names:

• chr12-4574300-A-C
• rs10774241
• NM_001394779.1:c.132+6252A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001394779.1(DYRK4):​c.132+6252A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 151,088 control chromosomes in the GnomAD database, including 9 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 0.0046 (9 hom., cov: 28)
• Consequence: DYRK4 NM_001394779.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYRK4	NM_001394779.1	c.132+6252A>C		intron_variant	Intron 2 of 14	ENST00000543431.6	NP_001381708.1
DYRK4	NM_001371301.2	c.132+6252A>C		intron_variant	Intron 2 of 14		NP_001358230.1
DYRK4	NM_001394780.1	c.114+944A>C		intron_variant	Intron 2 of 14		NP_001381709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYRK4	ENST00000543431.6	c.132+6252A>C		intron_variant	Intron 2 of 14	5	NM_001394779.1	ENSP00000439697.2

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 698 AN: 150978 Hom.: 9 Cov.: 28

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.0563

Gnomad AMR AF: 0.00310

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.000879

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00724

Gnomad OTH AF: 0.00528

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

GnomAD4 genome AF: 0.00462 AC: 698 AN: 151088 Hom.: 9 Cov.: 28 AF XY: 0.00421 AC XY: 310 AN XY: 73670

African (AFR) AF: 0.00178 AC: 73 AN: 41004

American (AMR) AF: 0.00309 AC: 47 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4794

European-Finnish (FIN) AF: 0.000879 AC: 9 AN: 10244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00724 AC: 492 AN: 67962

Other (OTH) AF: 0.00523 AC: 11 AN: 2102

Alfa AF: 0.0000342 Hom.: 77258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.57
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs10774241; hg19: chr12-4683466;