4-25252373-C-T

Position:

• chr4-25252373-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

PI4K2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.321C>T	p.Ala107Ala	synonymous_variant	2/10	ENST00000264864.8	NP_060793.2

Ensembl

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

GnomAD3 exomes AF: 0.825 AC: 207258 AN: 251276 Hom.: 85771 AF XY: 0.827 AC XY: 112330 AN XY: 135826

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 SAS exome AF: 0.816

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

Gnomad4 AFR exome AF: 0.802

Gnomad4 AMR exome AF: 0.812

Gnomad4 ASJ exome AF: 0.845

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.821

Gnomad4 FIN exome AF: 0.867

Gnomad4 NFE exome AF: 0.842

Gnomad4 OTH exome AF: 0.835

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

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.835

Alfa AF: 0.838 Hom.: 68142

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

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

Publications

LitVar

Other links and lift over

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