4-25260610-TTATATATATATATATATATATA-TTATATATATATATATA

Variant names:

• chr4-25260610-TTATATA-T
• rs533544057
• NM_018323.4:c.978+46_978+51delTATATA

Variant summary

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

The NM_018323.4(PI4K2B):​c.978+46_978+51delTATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 306,114 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0058 (1 hom., cov: 12)
  • Exomes 𝑓: 0.0046 (1 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: Uncertain_significance. The variant received 0 ACMG points.

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+46_978+51delTATATA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+46_1124+51delTATATA		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+25delTATATA		intron	N/A	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.978+20_978+25delTATATA		intron	N/A	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.963+20_963+25delTATATA		intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.00576 AC: 778 AN: 135048 Hom.: 1 Cov.: 12

Gnomad AFR AF: 0.00694

Gnomad AMI AF: 0.0405

Gnomad AMR AF: 0.00492

Gnomad ASJ AF: 0.00814

Gnomad EAS AF: 0.00526

Gnomad SAS AF: 0.00548

Gnomad FIN AF: 0.00152

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.00509

Gnomad OTH AF: 0.00872

GnomAD2 exomes AF: 0.00260 AC: 96 AN: 36926 AF XY: 0.00272

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.000820

Gnomad ASJ exome AF: 0.00529

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00418

Gnomad NFE exome AF: 0.00227

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00462 AC: 791 AN: 171054 Hom.: 1 AF XY: 0.00487 AC XY: 463 AN XY: 95094

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

African (AFR) AF: 0.00325 AC: 13 AN: 4002

American (AMR) AF: 0.00438 AC: 31 AN: 7082

Ashkenazi Jewish (ASJ) AF: 0.00353 AC: 19 AN: 5388

East Asian (EAS) AF: 0.00496 AC: 42 AN: 8470

South Asian (SAS) AF: 0.00237 AC: 18 AN: 7582

European-Finnish (FIN) AF: 0.00270 AC: 66 AN: 24488

Middle Eastern (MID) AF: 0.00163 AC: 1 AN: 614

European-Non Finnish (NFE) AF: 0.00533 AC: 557 AN: 104524

Other (OTH) AF: 0.00494 AC: 44 AN: 8904

⚠️ 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: 0.00577 AC: 779 AN: 135060 Hom.: 1 Cov.: 12 AF XY: 0.00565 AC XY: 365 AN XY: 64590

African (AFR) AF: 0.00696 AC: 252 AN: 36232

American (AMR) AF: 0.00492 AC: 64 AN: 13006

Ashkenazi Jewish (ASJ) AF: 0.00814 AC: 27 AN: 3316

East Asian (EAS) AF: 0.00528 AC: 24 AN: 4544

South Asian (SAS) AF: 0.00550 AC: 23 AN: 4180

European-Finnish (FIN) AF: 0.00152 AC: 10 AN: 6596

Middle Eastern (MID) AF: 0.00379 AC: 1 AN: 264

European-Non Finnish (NFE) AF: 0.00509 AC: 327 AN: 64210

Other (OTH) AF: 0.00866 AC: 16 AN: 1848

Alfa AF: 0.00 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs533544057; hg19: chr4-25262232;