Genetic Variant PI4K2B:c.978+50_978+51delTA (chr4-25260610-TTA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_018323.4(PI4K2B):c.978+50_978+51delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 305,644 control chromosomes in the GnomAD database, including 81 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 80 hom., cov: 12)

Exomes 𝑓: 0.0070 ( 1 hom. )

Consequence

PI4K2B
NM_018323.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0190

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0321 (4331/134858) while in subpopulation AFR AF = 0.0389 (1408/36174). AF 95% confidence interval is 0.0372. There are 80 homozygotes in GnomAd4. There are 2043 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 80 AR gene

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.978+50_978+51delTA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+50_1124+51delTA		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.978+20_978+21delTA	intron	N/A	ENSP00000264864.6	Q8TCG2
PI4K2B	ENST00000871538.1		c.978+20_978+21delTA	intron	N/A	ENSP00000541597.1
PI4K2B	ENST00000963199.1		c.963+20_963+21delTA	intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4326

AN:

134844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0389

Gnomad AMI

AF:

0.0150

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.0249

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0280

Gnomad NFE

AF:

0.0315

Gnomad OTH

AF:

0.0354

GnomAD4 exome

AF:

0.00697

AC:

1190

AN:

170786

Hom.:

AF XY:

0.00717

AC XY:

681

AN XY:

94990

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00525

AC:

AN:

3998

American (AMR)

AF:

0.00681

AC:

AN:

7052

Ashkenazi Jewish (ASJ)

AF:

0.00632

AC:

AN:

5376

East Asian (EAS)

AF:

0.00639

AC:

AN:

8454

South Asian (SAS)

AF:

0.00290

AC:

AN:

7584

European-Finnish (FIN)

AF:

0.00488

AC:

119

AN:

24368

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

612

European-Non Finnish (NFE)

AF:

0.00783

AC:

818

AN:

104436

Other (OTH)

AF:

0.00752

AC:

AN:

8906

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.309

Heterozygous variant carriers

185

278

370

463

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:

0.0321

AC:

4331

AN:

134858

Hom.:

Cov.:

AF XY:

0.0317

AC XY:

2043

AN XY:

64510

show subpopulations

African (AFR)

AF:

0.0389

AC:

1408

AN:

36174

American (AMR)

AF:

0.0239

AC:

310

AN:

12988

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

101

AN:

3314

East Asian (EAS)

AF:

0.0280

AC:

127

AN:

4538

South Asian (SAS)

AF:

0.0245

AC:

102

AN:

4168

European-Finnish (FIN)

AF:

0.0261

AC:

172

AN:

6584

Middle Eastern (MID)

AF:

0.0303

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0315

AC:

2020

AN:

64114

Other (OTH)

AF:

0.0378

AC:

AN:

1850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

157

314

470

627

784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0180

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.019

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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4-25260610-TTATATATATATATATATATATA-TTATATATATATATATATATA

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