4-25234216-C-T

Variant names:

• chr4-25234216-C-T
• rs1057456837
• NM_018323.4:c.53C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018323.4(PI4K2B):​c.53C>T​(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,411,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: PI4K2B NM_018323.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058760434).

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.53C>T	p.Pro18Leu	missense	Exon 1 of 10	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.184C>T		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.53C>T	p.Pro18Leu	missense	Exon 1 of 10	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.53C>T	p.Pro18Leu	missense	Exon 1 of 11	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.53C>T	p.Pro18Leu	missense	Exon 1 of 10	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152092 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00 AC: 0 AN: 50362 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000238 AC: 3 AN: 1259732 Hom.: 0 Cov.: 30 AF XY: 0.00000162 AC XY: 1 AN XY: 615978

African (AFR) AF: 0.00 AC: 0 AN: 25742

American (AMR) AF: 0.0000489 AC: 1 AN: 20456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19928

East Asian (EAS) AF: 0.00 AC: 0 AN: 28088

South Asian (SAS) AF: 0.00 AC: 0 AN: 62210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4406

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1013718

Other (OTH) AF: 0.0000387 AC: 2 AN: 51728

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152092 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67990

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-0.17
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.038
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.050
MutPred		0.21		Gain of glycosylation at S17 (P = 0.0076)
MVP		0.15
MPC		0.33
ClinPred		0.18	T
GERP RS		0.53
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.045
gMVP		0.061
Mutation Taster		=92/8	polymorphism

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: rs1057456837; hg19: chr4-25235838;