4-25260610-TTATATATATATATATATATA-TTATATATATATATATA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.978+48_978+51delTATA		intron_variant	Intron 6 of 9	ENST00000264864.8	NP_060793.2
PI4K2B	XM_005248174.3	c.963+48_963+51delTATA		intron_variant	Intron 6 of 9		XP_005248231.1
PI4K2B	XM_005248175.5	c.690+48_690+51delTATA		intron_variant	Intron 6 of 9		XP_005248232.1
PI4K2B	NR_144633.2	n.1124+48_1124+51delTATA		intron_variant	Intron 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2B	ENST00000264864.8	c.978+20_978+23delTATA		intron_variant	Intron 6 of 9	1	NM_018323.4	ENSP00000264864.6
PI4K2B	ENST00000512921.4	c.690+20_690+23delTATA		intron_variant	Intron 6 of 9	2		ENSP00000423373.1

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

GnomAD3 exomes AF: 0.0117 AC: 431 AN: 36926 Hom.: 0 AF XY: 0.0116 AC XY: 227 AN XY: 19504

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 SAS exome AF: 0.00906

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

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00970

Gnomad4 EAS exome AF: 0.0288

Gnomad4 SAS exome AF: 0.00620

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0153

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

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0660

Gnomad4 ASJ AF: 0.0521

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0600

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.0590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs533544057; hg19: chr4-25262232;