4-25260610-TTATATATATATATATATATATA-TTATATATATATATATATATATATA

Variant names:

• chr4-25260610-T-TTA
• rs533544057
• NM_018323.4:c.978+50_978+51dupTA

Variant summary

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

The NM_018323.4(PI4K2B):​c.978+50_978+51dupTA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (284 hom., cov: 12)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: PI4K2B NM_018323.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• 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 (NFE) allele frequency at 95% confidence interval = 0.0672 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+50_978+51dupTA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+50_1124+51dupTA		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+19_978+20insTA		intron	N/A	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.978+19_978+20insTA		intron	N/A	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.963+19_963+20insTA		intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 8744 AN: 134448 Hom.: 283 Cov.: 12

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.0232

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.0780

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0544

GnomAD4 exome AF: 0.00354 AC: 606 AN: 171116 Hom.: 0 Cov.: 0 AF XY: 0.00366 AC XY: 348 AN XY: 95168

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

African (AFR) AF: 0.00350 AC: 14 AN: 4002

American (AMR) AF: 0.00297 AC: 21 AN: 7078

Ashkenazi Jewish (ASJ) AF: 0.00408 AC: 22 AN: 5392

East Asian (EAS) AF: 0.00520 AC: 44 AN: 8464

South Asian (SAS) AF: 0.00119 AC: 9 AN: 7588

European-Finnish (FIN) AF: 0.00389 AC: 95 AN: 24398

Middle Eastern (MID) AF: 0.00162 AC: 1 AN: 618

European-Non Finnish (NFE) AF: 0.00359 AC: 376 AN: 104656

Other (OTH) AF: 0.00269 AC: 24 AN: 8920

⚠️ 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: 0.0650 AC: 8741 AN: 134460 Hom.: 284 Cov.: 12 AF XY: 0.0624 AC XY: 4016 AN XY: 64316

African (AFR) AF: 0.0635 AC: 2288 AN: 36052

American (AMR) AF: 0.0672 AC: 870 AN: 12948

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 352 AN: 3286

East Asian (EAS) AF: 0.0619 AC: 280 AN: 4524

South Asian (SAS) AF: 0.0600 AC: 250 AN: 4170

European-Finnish (FIN) AF: 0.0234 AC: 154 AN: 6580

Middle Eastern (MID) AF: 0.0769 AC: 20 AN: 260

European-Non Finnish (NFE) AF: 0.0689 AC: 4408 AN: 63944

Other (OTH) AF: 0.0540 AC: 99 AN: 1834

Alfa AF: 0.0196 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.019
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV53513722;