rs6073604

Positions:

• chr20-45023486-G-A

Variant summary

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

The NM_006282.5(STK4):​c.1148-1487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,138 control chromosomes in the GnomAD database, including 58,075 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 0.87 (58075 hom., cov: 30)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

Genes affected

STK4 (HGNC:11408): (serine/threonine kinase 4) The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK4	NM_006282.5	c.1148-1487G>A		intron_variant		ENST00000372806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK4	ENST00000372806.8	c.1148-1487G>A		intron_variant		1	NM_006282.5	P1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132653 AN: 152020 Hom.: 58021 Cov.: 30

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.873 AC: 132767 AN: 152138 Hom.: 58075 Cov.: 30 AF XY: 0.876 AC XY: 65201 AN XY: 74390

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.866

Alfa AF: 0.846 Hom.: 58973

Bravo AF: 0.872

Asia WGS AF: 0.926 AC: 3221 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	6.5
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6073604; hg19: chr20-43652127;