NM_018323.4:c.978+48_978+51dupTATA

Variant names:

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

Variant summary

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

The NM_018323.4(PI4K2B):​c.978+48_978+51dupTATA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (18 hom., cov: 12)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: PI4K2B NM_018323.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• 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 sas. GnomAd4 allele frequency = 0.0152 (2048/134850) while in subpopulation SAS AF = 0.0247 (103/4166). AF 95% confidence interval is 0.0209. There are 18 homozygotes in GnomAd4. There are 949 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 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+48_978+51dupTATA		intron	N/A	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.1124+48_1124+51dupTATA		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+19_978+20insTATA		intron	N/A	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.978+19_978+20insTATA		intron	N/A	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.963+19_963+20insTATA		intron	N/A	ENSP00000633258.1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2046 AN: 134838 Hom.: 18 Cov.: 12

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0105

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00364

Gnomad MID AF: 0.0246

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0174

GnomAD4 exome AF: 0.00100 AC: 172 AN: 171394 Hom.: 0 Cov.: 0 AF XY: 0.000986 AC XY: 94 AN XY: 95324

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

African (AFR) AF: 0.00150 AC: 6 AN: 4006

American (AMR) AF: 0.000705 AC: 5 AN: 7092

Ashkenazi Jewish (ASJ) AF: 0.000371 AC: 2 AN: 5396

East Asian (EAS) AF: 0.000589 AC: 5 AN: 8484

South Asian (SAS) AF: 0.000395 AC: 3 AN: 7594

European-Finnish (FIN) AF: 0.00249 AC: 61 AN: 24472

Middle Eastern (MID) AF: 0.00163 AC: 1 AN: 614

European-Non Finnish (NFE) AF: 0.000811 AC: 85 AN: 104812

Other (OTH) AF: 0.000448 AC: 4 AN: 8924

⚠️ 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: 0.0152 AC: 2048 AN: 134850 Hom.: 18 Cov.: 12 AF XY: 0.0147 AC XY: 949 AN XY: 64486

African (AFR) AF: 0.0139 AC: 502 AN: 36174

American (AMR) AF: 0.0130 AC: 169 AN: 13000

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 62 AN: 3314

East Asian (EAS) AF: 0.0106 AC: 48 AN: 4536

South Asian (SAS) AF: 0.0247 AC: 103 AN: 4166

European-Finnish (FIN) AF: 0.00364 AC: 24 AN: 6592

Middle Eastern (MID) AF: 0.0267 AC: 7 AN: 262

European-Non Finnish (NFE) AF: 0.0167 AC: 1069 AN: 64100

Other (OTH) AF: 0.0173 AC: 32 AN: 1848

Alfa AF: 0.00256 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.019
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;