ENST00000512921.4:c.-21+7810G>A

Variant names:

• chr4-25168563-G-A
• rs2133508
• ENST00000512921.4:c.-21+7810G>A

Variant summary

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

The ENST00000512921.4(PI4K2B):​c.-21+7810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,208 control chromosomes in the GnomAD database, including 782 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 0.087 (782 hom., cov: 31)
• Consequence: PI4K2B ENST00000512921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPSECS-DT	NR_037934.1	n.82+7810G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2B	ENST00000512921.4	c.-21+7810G>A		intron_variant	Intron 1 of 9	2		ENSP00000423373.1
SEPSECS-AS1	ENST00000507794.2	n.82+7810G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13168 AN: 152090 Hom.: 783 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0866 AC: 13188 AN: 152208 Hom.: 782 Cov.: 31 AF XY: 0.0865 AC XY: 6441 AN XY: 74422

African (AFR) AF: 0.172 AC: 7153 AN: 41496

American (AMR) AF: 0.0482 AC: 737 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.149 AC: 772 AN: 5176

South Asian (SAS) AF: 0.103 AC: 495 AN: 4824

European-Finnish (FIN) AF: 0.0276 AC: 293 AN: 10602

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3012 AN: 68022

Other (OTH) AF: 0.0867 AC: 183 AN: 2110

Alfa AF: 0.0591 Hom.: 183

Bravo AF: 0.0918

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.74
PhyloP100		-0.67
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: rs2133508; hg19: chr4-25170185;