4-25234173-C-A

Variant names:

• chr4-25234173-C-A
• rs863223383
• NM_018323.4:c.10C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_018323.4(PI4K2B):​c.10C>A​(p.Pro4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000816 in 1,225,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: PI4K2B NM_018323.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.624
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05494526).
• BP6: Variant 4-25234173-C-A is Benign according to our data. Variant chr4-25234173-C-A is described in ClinVar as Benign. ClinVar VariationId is 208927.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018323.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	NM_018323.4	MANE Select	c.10C>A	p.Pro4Thr	missense	Exon 1 of 10	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.141C>A		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.10C>A	p.Pro4Thr	missense	Exon 1 of 10	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.10C>A	p.Pro4Thr	missense	Exon 1 of 11	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.10C>A	p.Pro4Thr	missense	Exon 1 of 10	ENSP00000633258.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.16e-7 AC: 1 AN: 1225760 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 594868

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24968

American (AMR) AF: 0.00 AC: 0 AN: 15352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17414

East Asian (EAS) AF: 0.00 AC: 0 AN: 28058

South Asian (SAS) AF: 0.00 AC: 0 AN: 54536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4538

European-Non Finnish (NFE) AF: 0.00000100 AC: 1 AN: 996570

Other (OTH) AF: 0.00 AC: 0 AN: 49950

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Abnormality of neuronal migration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.62
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.043
Sift	Benign	0.072	T
Sift4G	Benign	0.66	T
Polyphen		0.035	B
Vest4		0.14
MutPred		0.30		Gain of glycosylation at S5 (P = 0.0017)
MVP		0.15
MPC		0.36
ClinPred		0.21	T
GERP RS		-7.6
PromoterAI		-0.090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.048
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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: rs863223383; hg19: chr4-25235795;