4-25260610-TTATATATATATATATATATATA-TTATATA

Variant names:

• chr4-25260610-TTATATATATATATATA-T
• rs533544057
• NM_018323.4:c.978+36_978+51delTATATATATATATATA

Variant summary

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

The NM_018323.4(PI4K2B):​c.978+36_978+51delTATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0079 in 306,796 control chromosomes in the GnomAD database, including 63 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (44 hom., cov: 12)
  • Exomes 𝑓: 0.0031 (19 hom.)
• Consequence: PI4K2B NM_018323.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68
• 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: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0533 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+36_978+51delTATATATATATATATA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+36_1124+51delTATATATATATATATA		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+35delTATATATATATATATA		intron	N/A	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.978+20_978+35delTATATATATATATATA		intron	N/A	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.963+20_963+35delTATATATATATATATA		intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 1883 AN: 135084 Hom.: 44 Cov.: 12

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000238

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0210

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.0136

GnomAD2 exomes AF: 0.00718 AC: 265 AN: 36926 AF XY: 0.00667

Gnomad AFR exome AF: 0.0745

Gnomad AMR exome AF: 0.00574

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000102

Gnomad NFE exome AF: 0.00166

Gnomad OTH exome AF: 0.0131

GnomAD4 exome AF: 0.00312 AC: 535 AN: 171700 Hom.: 19 AF XY: 0.00300 AC XY: 286 AN XY: 95490

African (AFR) AF: 0.0595 AC: 238 AN: 4002

American (AMR) AF: 0.00578 AC: 41 AN: 7094

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 84 AN: 5402

East Asian (EAS) AF: 0.00 AC: 0 AN: 8498

South Asian (SAS) AF: 0.000526 AC: 4 AN: 7598

European-Finnish (FIN) AF: 0.000163 AC: 4 AN: 24594

Middle Eastern (MID) AF: 0.00324 AC: 2 AN: 618

European-Non Finnish (NFE) AF: 0.000962 AC: 101 AN: 104962

Other (OTH) AF: 0.00683 AC: 61 AN: 8932

GnomAD4 genome AF: 0.0140 AC: 1888 AN: 135096 Hom.: 44 Cov.: 12 AF XY: 0.0138 AC XY: 891 AN XY: 64602

African (AFR) AF: 0.0471 AC: 1707 AN: 36244

American (AMR) AF: 0.00661 AC: 86 AN: 13010

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 42 AN: 3316

East Asian (EAS) AF: 0.00 AC: 0 AN: 4544

South Asian (SAS) AF: 0.000239 AC: 1 AN: 4180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6598

Middle Eastern (MID) AF: 0.0227 AC: 6 AN: 264

European-Non Finnish (NFE) AF: 0.000327 AC: 21 AN: 64226

Other (OTH) AF: 0.0135 AC: 25 AN: 1850

Alfa AF: 0.00 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
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;