4-25260610-TTATATATATATATATATATATA-TTATATATATATA

Variant names:

• chr4-25260610-TTATATATATA-T
• rs533544057
• NM_018323.4:c.978+42_978+51delTATATATATA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018323.4(PI4K2B):​c.978+42_978+51delTATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 306,464 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (13 hom., cov: 12)
  • Exomes 𝑓: 0.0059 (11 hom.)
• Consequence: PI4K2B NM_018323.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 4-25260610-TTATATATATA-T is Benign according to our data. Variant chr4-25260610-TTATATATATA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2776149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0114 (1542/135078) while in subpopulation AFR AF = 0.0161 (585/36248). AF 95% confidence interval is 0.0151. There are 13 homozygotes in GnomAd4. There are 750 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 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+42_978+51delTATATATATA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+42_1124+51delTATATATATA		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+29delTATATATATA		intron	N/A	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.978+20_978+29delTATATATATA		intron	N/A	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.963+20_963+29delTATATATATA		intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1542 AN: 135066 Hom.: 13 Cov.: 12

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0278

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0145

Gnomad EAS AF: 0.00395

Gnomad SAS AF: 0.0107

Gnomad FIN AF: 0.00137

Gnomad MID AF: 0.0175

Gnomad NFE AF: 0.00982

Gnomad OTH AF: 0.0169

GnomAD2 exomes AF: 0.00401 AC: 148 AN: 36926 AF XY: 0.00379

Gnomad AFR exome AF: 0.00363

Gnomad AMR exome AF: 0.00369

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.000996

Gnomad FIN exome AF: 0.000815

Gnomad NFE exome AF: 0.00553

Gnomad OTH exome AF: 0.00746

GnomAD4 exome AF: 0.00595 AC: 1019 AN: 171386 Hom.: 11 AF XY: 0.00596 AC XY: 568 AN XY: 95292

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

African (AFR) AF: 0.00623 AC: 25 AN: 4014

American (AMR) AF: 0.00452 AC: 32 AN: 7086

Ashkenazi Jewish (ASJ) AF: 0.00984 AC: 53 AN: 5386

East Asian (EAS) AF: 0.00200 AC: 17 AN: 8494

South Asian (SAS) AF: 0.00356 AC: 27 AN: 7594

European-Finnish (FIN) AF: 0.00106 AC: 26 AN: 24568

Middle Eastern (MID) AF: 0.0146 AC: 9 AN: 618

European-Non Finnish (NFE) AF: 0.00719 AC: 753 AN: 104698

Other (OTH) AF: 0.00862 AC: 77 AN: 8928

⚠️ 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: 0.0114 AC: 1542 AN: 135078 Hom.: 13 Cov.: 12 AF XY: 0.0116 AC XY: 750 AN XY: 64600

African (AFR) AF: 0.0161 AC: 585 AN: 36248

American (AMR) AF: 0.0112 AC: 146 AN: 13006

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 48 AN: 3318

East Asian (EAS) AF: 0.00396 AC: 18 AN: 4540

South Asian (SAS) AF: 0.0108 AC: 45 AN: 4180

European-Finnish (FIN) AF: 0.00137 AC: 9 AN: 6592

Middle Eastern (MID) AF: 0.0189 AC: 5 AN: 264

European-Non Finnish (NFE) AF: 0.00983 AC: 631 AN: 64216

Other (OTH) AF: 0.0168 AC: 31 AN: 1850

Alfa AF: 0.00 Hom.: 22

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;