chr4-25260610-TTATA-T

Variant names:

• chr4-25260610-TTATA-T
• rs533544057
• NM_018323.4:c.978+48_978+51delTATA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018323.4(PI4K2B):​c.978+48_978+51delTATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 304,288 control chromosomes in the GnomAD database, including 333 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (328 hom., cov: 12)
  • Exomes 𝑓: 0.016 (5 hom.)
• Consequence: PI4K2B NM_018323.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

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+48_978+51delTATA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+48_1124+51delTATA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.978+20_978+23delTATA		intron	N/A	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.978+20_978+23delTATA		intron	N/A	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.963+20_963+23delTATA		intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 8651 AN: 134710 Hom.: 327 Cov.: 12

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0600

Gnomad MID AF: 0.0634

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.0573

GnomAD2 exomes AF: 0.0117 AC: 431 AN: 36926 AF XY: 0.0116

Gnomad AFR exome AF: 0.00282

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00740

Gnomad EAS exome AF: 0.00747

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.00786

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.0162 AC: 2744 AN: 169568 Hom.: 5 AF XY: 0.0164 AC XY: 1546 AN XY: 94344

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

African (AFR) AF: 0.0105 AC: 42 AN: 3990

American (AMR) AF: 0.0107 AC: 75 AN: 7040

Ashkenazi Jewish (ASJ) AF: 0.00970 AC: 52 AN: 5360

East Asian (EAS) AF: 0.0288 AC: 242 AN: 8416

South Asian (SAS) AF: 0.00620 AC: 47 AN: 7578

European-Finnish (FIN) AF: 0.0163 AC: 391 AN: 23940

Middle Eastern (MID) AF: 0.0164 AC: 10 AN: 610

European-Non Finnish (NFE) AF: 0.0169 AC: 1750 AN: 103810

Other (OTH) AF: 0.0153 AC: 135 AN: 8824

⚠️ 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.

GnomAD4 genome AF: 0.0642 AC: 8648 AN: 134720 Hom.: 328 Cov.: 12 AF XY: 0.0635 AC XY: 4094 AN XY: 64422

African (AFR) AF: 0.0313 AC: 1133 AN: 36186

American (AMR) AF: 0.0660 AC: 856 AN: 12966

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 172 AN: 3304

East Asian (EAS) AF: 0.100 AC: 453 AN: 4530

South Asian (SAS) AF: 0.113 AC: 472 AN: 4176

European-Finnish (FIN) AF: 0.0600 AC: 395 AN: 6578

Middle Eastern (MID) AF: 0.0611 AC: 16 AN: 262

European-Non Finnish (NFE) AF: 0.0768 AC: 4919 AN: 64016

Other (OTH) AF: 0.0590 AC: 109 AN: 1846

Alfa AF: 0.0357 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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: rs533544057; hg19: chr4-25262232;