chr4-25252407-G-T

Variant names:

• chr4-25252407-G-T
• rs761511829
• NM_018323.4:c.355G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018323.4(PI4K2B):​c.355G>T​(p.Val119Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PI4K2B NM_018323.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035421103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.355G>T	p.Val119Phe	missense_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.355G>T	p.Val119Phe	missense_variant	Exon 2 of 10	1	NM_018323.4	ENSP00000264864.6
PI4K2B	ENST00000512921.4	c.67G>T	p.Val23Phe	missense_variant	Exon 2 of 10	2		ENSP00000423373.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251324 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135846

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459010 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.0080	.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.92	.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.084
Sift	Benign	0.090	T;T
Sift4G	Benign	0.068	T;T
Polyphen		0.0	.;B
Vest4		0.12
MutPred		0.26		.;Gain of sheet (P = 0.039);
MVP		0.17
MPC		0.42
ClinPred		0.073	T
GERP RS		-5.0
Varity_R		0.044
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761511829; hg19: chr4-25254029;