4-25260610-TTATATATATATATATATATA-TTATATATATATATATATA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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.

• 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 male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 80 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.978+50_978+51delTA		intron_variant	Intron 6 of 9	ENST00000264864.8	NP_060793.2
PI4K2B	XM_005248174.3	c.963+50_963+51delTA		intron_variant	Intron 6 of 9		XP_005248231.1
PI4K2B	XM_005248175.5	c.690+50_690+51delTA		intron_variant	Intron 6 of 9		XP_005248232.1
PI4K2B	NR_144633.2	n.1124+50_1124+51delTA		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+21delTA		intron_variant	Intron 6 of 9	1	NM_018323.4	ENSP00000264864.6
PI4K2B	ENST00000512921.4	c.690+20_690+21delTA		intron_variant	Intron 6 of 9	2		ENSP00000423373.1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4326 AN: 134844 Hom.: 79 Cov.: 12

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.: 1 AF XY: 0.00717 AC XY: 681 AN XY: 94990

Gnomad4 AFR exome AF: 0.00525

Gnomad4 AMR exome AF: 0.00681

Gnomad4 ASJ exome AF: 0.00632

Gnomad4 EAS exome AF: 0.00639

Gnomad4 SAS exome AF: 0.00290

Gnomad4 FIN exome AF: 0.00488

Gnomad4 NFE exome AF: 0.00783

Gnomad4 OTH exome AF: 0.00752

GnomAD4 genome AF: 0.0321 AC: 4331 AN: 134858 Hom.: 80 Cov.: 12 AF XY: 0.0317 AC XY: 2043 AN XY: 64510

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0280

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.0315

Gnomad4 OTH AF: 0.0378

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;