NM_018323.4:c.978+40_978+51delTATATATATATA

Variant names:

• chr4-25260610-TTATATATATATA-T
• rs533544057
• NM_018323.4:c.978+40_978+51delTATATATATATA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018323.4(PI4K2B):​c.978+40_978+51delTATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 306,586 control chromosomes in the GnomAD database, including 52 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 0.016 (33 hom., cov: 12)
  • Exomes 𝑓: 0.011 (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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.016 (2157/135092) while in subpopulation AFR AF = 0.0263 (954/36252). AF 95% confidence interval is 0.0249. There are 33 homozygotes in GnomAd4. There are 1034 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

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+40_978+51delTATATATATATA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+40_1124+51delTATATATATATA		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+31delTATATATATATA		intron	N/A	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.978+20_978+31delTATATATATATA		intron	N/A	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.963+20_963+31delTATATATATATA		intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2153 AN: 135080 Hom.: 32 Cov.: 12

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.00926

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00263

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.00864

Gnomad MID AF: 0.0315

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.0169

GnomAD2 exomes AF: 0.00699 AC: 258 AN: 36926 AF XY: 0.00651

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.00861

Gnomad ASJ exome AF: 0.00423

Gnomad EAS exome AF: 0.000996

Gnomad FIN exome AF: 0.00652

Gnomad NFE exome AF: 0.00780

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.0106 AC: 1813 AN: 171494 Hom.: 19 AF XY: 0.0104 AC XY: 988 AN XY: 95370

African (AFR) AF: 0.0192 AC: 77 AN: 4010

American (AMR) AF: 0.00987 AC: 70 AN: 7094

Ashkenazi Jewish (ASJ) AF: 0.00815 AC: 44 AN: 5398

East Asian (EAS) AF: 0.00224 AC: 19 AN: 8496

South Asian (SAS) AF: 0.00514 AC: 39 AN: 7592

European-Finnish (FIN) AF: 0.00875 AC: 215 AN: 24562

Middle Eastern (MID) AF: 0.0194 AC: 12 AN: 618

European-Non Finnish (NFE) AF: 0.0116 AC: 1214 AN: 104800

Other (OTH) AF: 0.0138 AC: 123 AN: 8924

GnomAD4 genome AF: 0.0160 AC: 2157 AN: 135092 Hom.: 33 Cov.: 12 AF XY: 0.0160 AC XY: 1034 AN XY: 64604

African (AFR) AF: 0.0263 AC: 954 AN: 36252

American (AMR) AF: 0.0189 AC: 246 AN: 13012

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

East Asian (EAS) AF: 0.00264 AC: 12 AN: 4544

South Asian (SAS) AF: 0.0103 AC: 43 AN: 4180

European-Finnish (FIN) AF: 0.00864 AC: 57 AN: 6596

Middle Eastern (MID) AF: 0.0303 AC: 8 AN: 264

European-Non Finnish (NFE) AF: 0.0118 AC: 757 AN: 64214

Other (OTH) AF: 0.0162 AC: 30 AN: 1850

Alfa AF: 0.00875 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

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;