4-25252373-C-T

Variant names:

• chr4-25252373-C-T
• rs313567
• NM_018323.4:c.321C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018323.4(PI4K2B):​c.321C>T​(p.Ala107Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,607,196 control chromosomes in the GnomAD database, including 561,157 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51772 hom., cov: 32)
  • Exomes 𝑓: 0.84 (509385 hom.)
• Consequence: PI4K2B NM_018323.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 18 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.321C>T	p.Ala107Ala	synonymous_variant	Exon 2 of 10	ENST00000264864.8	NP_060793.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2B	ENST00000264864.8	c.321C>T	p.Ala107Ala	synonymous_variant	Exon 2 of 10	1	NM_018323.4	ENSP00000264864.6
PI4K2B	ENST00000512921.4	c.33C>T	p.Ala11Ala	synonymous_variant	Exon 2 of 10	2		ENSP00000423373.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125314 AN: 152018 Hom.: 51738 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.837

GnomAD2 exomes AF: 0.825 AC: 207258 AN: 251276 AF XY: 0.827

Gnomad AFR exome AF: 0.802

Gnomad AMR exome AF: 0.814

Gnomad ASJ exome AF: 0.847

Gnomad EAS exome AF: 0.701

Gnomad FIN exome AF: 0.866

Gnomad NFE exome AF: 0.843

Gnomad OTH exome AF: 0.836

GnomAD4 exome AF: 0.836 AC: 1216496 AN: 1455060 Hom.: 509385 Cov.: 31 AF XY: 0.836 AC XY: 605529 AN XY: 724362

African (AFR) AF: 0.802 AC: 26744 AN: 33354

American (AMR) AF: 0.812 AC: 36259 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 22045 AN: 26092

East Asian (EAS) AF: 0.713 AC: 28256 AN: 39650

South Asian (SAS) AF: 0.821 AC: 70686 AN: 86098

European-Finnish (FIN) AF: 0.867 AC: 46279 AN: 53400

Middle Eastern (MID) AF: 0.815 AC: 4697 AN: 5760

European-Non Finnish (NFE) AF: 0.842 AC: 931245 AN: 1105834

Other (OTH) AF: 0.835 AC: 50285 AN: 60194

GnomAD4 genome AF: 0.824 AC: 125394 AN: 152136 Hom.: 51772 Cov.: 32 AF XY: 0.824 AC XY: 61277 AN XY: 74364

African (AFR) AF: 0.803 AC: 33325 AN: 41490

American (AMR) AF: 0.810 AC: 12394 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2931 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3557 AN: 5154

South Asian (SAS) AF: 0.819 AC: 3944 AN: 4818

European-Finnish (FIN) AF: 0.861 AC: 9120 AN: 10588

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57268 AN: 68010

Other (OTH) AF: 0.835 AC: 1760 AN: 2108

Alfa AF: 0.838 Hom.: 83808

Bravo AF: 0.823

Asia WGS AF: 0.747 AC: 2599 AN: 3478

EpiCase AF: 0.845

EpiControl AF: 0.847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.8
DANN	Benign	0.29
PhyloP100		0.0040
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs313567; hg19: chr4-25253995; COSMIC: COSV53512438; COSMIC: COSV53512438;