4-25260610-TTATATATATA-T

Variant names:

• chr4-25260610-TTATATATATA-T
• rs533544057
• NM_018323.4:c.978+42_978+51delTATATATATA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018323.4(PI4K2B):​c.978+42_978+51delTATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 306,464 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (13 hom., cov: 12)
  • Exomes 𝑓: 0.0059 (11 hom.)
• Consequence: PI4K2B NM_018323.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.68

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 4-25260610-TTATATATATA-T is Benign according to our data. Variant chr4-25260610-TTATATATATA-T is described in ClinVar as [Likely_benign]. Clinvar id is 2776149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1542/135078) while in subpopulation AFR AF= 0.0161 (585/36248). AF 95% confidence interval is 0.0151. There are 13 homozygotes in gnomad4. There are 750 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.978+42_978+51delTATATATATA		intron_variant	Intron 6 of 9	ENST00000264864.8	NP_060793.2
PI4K2B	XM_005248174.3	c.963+42_963+51delTATATATATA		intron_variant	Intron 6 of 9		XP_005248231.1
PI4K2B	XM_005248175.5	c.690+42_690+51delTATATATATA		intron_variant	Intron 6 of 9		XP_005248232.1
PI4K2B	NR_144633.2	n.1124+42_1124+51delTATATATATA		intron_variant	Intron 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2B	ENST00000264864.8	c.978+20_978+29delTATATATATA		intron_variant	Intron 6 of 9	1	NM_018323.4	ENSP00000264864.6
PI4K2B	ENST00000512921.4	c.690+20_690+29delTATATATATA		intron_variant	Intron 6 of 9	2		ENSP00000423373.1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1542 AN: 135066 Hom.: 13 Cov.: 12

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0278

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0145

Gnomad EAS AF: 0.00395

Gnomad SAS AF: 0.0107

Gnomad FIN AF: 0.00137

Gnomad MID AF: 0.0175

Gnomad NFE AF: 0.00982

Gnomad OTH AF: 0.0169

GnomAD3 exomes AF: 0.00401 AC: 148 AN: 36926 Hom.: 2 AF XY: 0.00379 AC XY: 74 AN XY: 19504

Gnomad AFR exome AF: 0.00363

Gnomad AMR exome AF: 0.00369

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.000996

Gnomad SAS exome AF: 0.00659

Gnomad FIN exome AF: 0.000815

Gnomad NFE exome AF: 0.00553

Gnomad OTH exome AF: 0.00746

GnomAD4 exome AF: 0.00595 AC: 1019 AN: 171386 Hom.: 11 AF XY: 0.00596 AC XY: 568 AN XY: 95292

Gnomad4 AFR exome AF: 0.00623

Gnomad4 AMR exome AF: 0.00452

Gnomad4 ASJ exome AF: 0.00984

Gnomad4 EAS exome AF: 0.00200

Gnomad4 SAS exome AF: 0.00356

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.00719

Gnomad4 OTH exome AF: 0.00862

GnomAD4 genome AF: 0.0114 AC: 1542 AN: 135078 Hom.: 13 Cov.: 12 AF XY: 0.0116 AC XY: 750 AN XY: 64600

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0145

Gnomad4 EAS AF: 0.00396

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00137

Gnomad4 NFE AF: 0.00983

Gnomad4 OTH AF: 0.0168

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs533544057; hg19: chr4-25262232;