rs4549170

Variant names:

• chr20-45061562-C-G
• rs4549170
• NM_006282.5:c.1306-13456C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-45061562-C-G
• chr20-45061562-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006282.5(STK4):​c.1306-13456C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 150,120 control chromosomes in the GnomAD database, including 21,790 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 0.53 (21790 hom., cov: 28)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 4 publications found

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]

STK4 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to STK4 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5	c.1306-13456C>G		intron_variant	Intron 10 of 10	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.1306-13456C>G		intron_variant	Intron 10 of 10	1	NM_006282.5	ENSP00000361892.3

Frequencies

GnomAD3 genomes AF: 0.525 AC: 78736 AN: 150006 Hom.: 21749 Cov.: 28

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.525 AC: 78828 AN: 150120 Hom.: 21790 Cov.: 28 AF XY: 0.523 AC XY: 38253 AN XY: 73160

African (AFR) AF: 0.683 AC: 27965 AN: 40940

American (AMR) AF: 0.371 AC: 5588 AN: 15062

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1739 AN: 3444

East Asian (EAS) AF: 0.240 AC: 1215 AN: 5064

South Asian (SAS) AF: 0.388 AC: 1830 AN: 4716

European-Finnish (FIN) AF: 0.582 AC: 5857 AN: 10068

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 32930 AN: 67544

Other (OTH) AF: 0.523 AC: 1090 AN: 2084

Alfa AF: 0.505 Hom.: 2373

Bravo AF: 0.512

Asia WGS AF: 0.361 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.56
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4549170; hg19: chr20-43690203;