rs2284271

Variant names:

• chr20-44976780-C-T
• rs2284271
• NM_006282.5:c.117-1663C>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.117-1663C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 152,130 control chromosomes in the GnomAD database, including 754 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 0.093 (754 hom., cov: 32)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5	c.117-1663C>T		intron_variant	Intron 2 of 10	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.117-1663C>T		intron_variant	Intron 2 of 10	1	NM_006282.5	ENSP00000361892.3

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14104 AN: 152012 Hom.: 753 Cov.: 32

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0612

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.0928 AC: 14111 AN: 152130 Hom.: 754 Cov.: 32 AF XY: 0.0964 AC XY: 7172 AN XY: 74364

African (AFR) AF: 0.0619 AC: 2571 AN: 41518

American (AMR) AF: 0.163 AC: 2494 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3470

East Asian (EAS) AF: 0.187 AC: 964 AN: 5168

South Asian (SAS) AF: 0.0620 AC: 299 AN: 4820

European-Finnish (FIN) AF: 0.100 AC: 1058 AN: 10564

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5955 AN: 67990

Other (OTH) AF: 0.121 AC: 255 AN: 2110

Alfa AF: 0.0951 Hom.: 1477

Bravo AF: 0.0982

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-1.1
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: rs2284271; hg19: chr20-43605421;