rs7271519

Positions:

• chr20-44998055-T-C

Variant summary

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

The NM_006282.5(STK4):​c.831+749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,072 control chromosomes in the GnomAD database, including 5,688 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 0.26 (5688 hom., cov: 32)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK4	NM_006282.5	c.831+749T>C		intron_variant		ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.831+749T>C		intron_variant		1	NM_006282.5	ENSP00000361892	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38985 AN: 151954 Hom.: 5684 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.256 AC: 39004 AN: 152072 Hom.: 5688 Cov.: 32 AF XY: 0.260 AC XY: 19289 AN XY: 74330

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.289

Alfa AF: 0.304 Hom.: 9419

Bravo AF: 0.236

Asia WGS AF: 0.135 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.81

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: rs7271519; hg19: chr20-43626696;