dbSNP rs1057456837: PI4K2B:p.Pro18Arg (chr4-25234216-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018323.4(PI4K2B):c.53C>G(p.Pro18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,411,824 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 (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PI4K2B
NM_018323.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.167

Publications

0 publications found

Variant links:

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]

PI4K2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08610979).

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>G	p.Pro18Arg	missense	Exon 1 of 10	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.184C>G		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.53C>G	p.Pro18Arg	missense	Exon 1 of 10	ENSP00000264864.6	Q8TCG2
PI4K2B	ENST00000871538.1		c.53C>G	p.Pro18Arg	missense	Exon 1 of 11	ENSP00000541597.1
PI4K2B	ENST00000963199.1		c.53C>G	p.Pro18Arg	missense	Exon 1 of 10	ENSP00000633258.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.0000397

AC:

AN:

50362

AF XY:

0.0000689

show subpopulations

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:

0.0000999

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1259732

Hom.:

Cov.:

AF XY:

0.00000812

AC XY:

AN XY:

615978

show subpopulations

African (AFR)

AF:

0.000272

AC:

AN:

25742

American (AMR)

AF:

0.00

AC:

AN:

20456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19928

East Asian (EAS)

AF:

0.00

AC:

AN:

28088

South Asian (SAS)

AF:

0.00

AC:

AN:

62210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4406

European-Non Finnish (NFE)

AF:

0.00000592

AC:

AN:

1013718

Other (OTH)

AF:

0.00

AC:

AN:

51728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000642

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0075

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.41

M_CAP

Benign

0.074

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.17

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

REVEL

Benign

0.047

Sift

Uncertain

0.0070

Sift4G

Benign

0.39

Polyphen

0.57

Vest4

0.072

MutPred

0.21

Gain of glycosylation at S17 (P = 0.0076)

MVP

0.27

MPC

0.37

ClinPred

0.064

GERP RS

0.53

PromoterAI

0.017

Neutral

(source)

Varity_R

0.058

gMVP

0.11

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over