rs4810446

Variant names:

• chr20-44967227-T-A
• rs4810446
• NM_006282.5:c.35+624T>A

Your query was ambiguous. Multiple possible variants found:

• chr20-44967227-T-A
• chr20-44967227-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006282.5(STK4):​c.35+624T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 985,110 control chromosomes in the GnomAD database, including 3,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (755 hom., cov: 32)
  • Exomes 𝑓: 0.079 (2763 hom.)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30
• 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 -10 ACMG points.

• BP6: Variant 20-44967227-T-A is Benign according to our data. Variant chr20-44967227-T-A is described in ClinVar as Benign. ClinVar VariationId is 2688246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006282.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	NM_006282.5	MANE Select	c.35+624T>A		intron	N/A	NP_006273.1
	STK4	NM_001352385.2		c.35+624T>A		intron	N/A	NP_001339314.1
	STK4	NR_147974.2		n.92+624T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	ENST00000372806.8	TSL:1 MANE Select	c.35+624T>A		intron	N/A	ENSP00000361892.3
	STK4	ENST00000499879.8	TSL:1	c.35+624T>A		intron	N/A	ENSP00000443514.1
	STK4	ENST00000488618.2	TSL:1	n.91+624T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13784 AN: 152048 Hom.: 754 Cov.: 32

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0608

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0793 AC: 66039 AN: 832944 Hom.: 2763 Cov.: 29 AF XY: 0.0793 AC XY: 30495 AN XY: 384644

African (AFR) AF: 0.0610 AC: 963 AN: 15780

American (AMR) AF: 0.222 AC: 218 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 601 AN: 5150

East Asian (EAS) AF: 0.194 AC: 705 AN: 3630

South Asian (SAS) AF: 0.0633 AC: 1041 AN: 16458

European-Finnish (FIN) AF: 0.0652 AC: 18 AN: 276

Middle Eastern (MID) AF: 0.135 AC: 218 AN: 1620

European-Non Finnish (NFE) AF: 0.0784 AC: 59719 AN: 761752

Other (OTH) AF: 0.0936 AC: 2556 AN: 27294

GnomAD4 genome AF: 0.0906 AC: 13791 AN: 152166 Hom.: 755 Cov.: 32 AF XY: 0.0946 AC XY: 7037 AN XY: 74388

African (AFR) AF: 0.0606 AC: 2517 AN: 41524

American (AMR) AF: 0.178 AC: 2729 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 411 AN: 3466

East Asian (EAS) AF: 0.188 AC: 972 AN: 5168

South Asian (SAS) AF: 0.0615 AC: 296 AN: 4814

European-Finnish (FIN) AF: 0.0957 AC: 1013 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0808 AC: 5497 AN: 67994

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.0889 Hom.: 82

Bravo AF: 0.0994

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.8
DANN	Benign	0.91
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.37		Position offset: 2
DS_DG_spliceai		0.20		Position offset: 44

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

Other links and lift over

dbSNP: rs4810446; hg19: chr20-43595868;