4-25234351-A-G

Variant names:

• chr4-25234351-A-G
• rs1448460809
• NM_018323.4:c.188A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018323.4(PI4K2B):​c.188A>G​(p.Glu63Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,259,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E63A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: PI4K2B NM_018323.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

Genes affected

PI4K2B (HGNC:18215): (phosphatidylinositol 4-kinase type 2 beta) This gene encodes a member of the type II PI4 kinase protein family. The encoded protein is primarily cytosolic and contributes to overall PI4-kinase activity along with other protein family members. This protein is involved in early T cell activation. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.108872235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018323.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	NM_018323.4	MANE Select	c.188A>G	p.Glu63Gly	missense	Exon 1 of 10	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.319A>G		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.188A>G	p.Glu63Gly	missense	Exon 1 of 10	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.188A>G	p.Glu63Gly	missense	Exon 1 of 11	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.188A>G	p.Glu63Gly	missense	Exon 1 of 10	ENSP00000633258.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1259832 Hom.: 0 Cov.: 31 AF XY: 0.00000325 AC XY: 2 AN XY: 616204

African (AFR) AF: 0.00 AC: 0 AN: 26004

American (AMR) AF: 0.00 AC: 0 AN: 22098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20876

East Asian (EAS) AF: 0.00 AC: 0 AN: 27458

South Asian (SAS) AF: 0.00 AC: 0 AN: 63968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3678

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1013304

Other (OTH) AF: 0.00 AC: 0 AN: 51648

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.017
Sift	Benign	0.11	T
Sift4G	Benign	0.31	T
Polyphen		0.069	B
Vest4		0.18
MutPred		0.32		Loss of solvent accessibility (P = 0.0187)
MVP		0.38
MPC		0.41
ClinPred		0.12	T
GERP RS		0.54
PromoterAI		-0.016	Neutral
Varity_R		0.11
gMVP		0.32
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1448460809; hg19: chr4-25235973;