4-25168420-C-G

Variant names:

• chr4-25168420-C-G
• rs2133507
• ENST00000512921.4:c.-21+7667C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000512921.4(PI4K2B):​c.-21+7667C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,126 control chromosomes in the GnomAD database, including 51,265 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 (51265 hom., cov: 31)
• Consequence: PI4K2B ENST00000512921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 3 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]

SEPSECS-AS1 (HGNC:27737): (SEPSECS antisense RNA 1 (head to head))

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPSECS-DT	NR_037934.1	n.82+7667C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2B	ENST00000512921.4	c.-21+7667C>G		intron_variant	Intron 1 of 9	2		ENSP00000423373.1
SEPSECS-AS1	ENST00000507794.2	n.82+7667C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124771 AN: 152008 Hom.: 51238 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.831

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.821 AC: 124849 AN: 152126 Hom.: 51265 Cov.: 31 AF XY: 0.821 AC XY: 61041 AN XY: 74350

African (AFR) AF: 0.825 AC: 34253 AN: 41502

American (AMR) AF: 0.824 AC: 12601 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2963 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3457 AN: 5160

South Asian (SAS) AF: 0.851 AC: 4103 AN: 4822

European-Finnish (FIN) AF: 0.822 AC: 8691 AN: 10574

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.825 AC: 56066 AN: 67994

Other (OTH) AF: 0.829 AC: 1749 AN: 2110

Alfa AF: 0.827 Hom.: 6072

Bravo AF: 0.822

Asia WGS AF: 0.758 AC: 2634 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-0.51
Mutation Taster		=100/0	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: rs2133507; hg19: chr4-25170042;