1-164563088-T-C

Position:

• chr1-164563088-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002585.4(PBX1):​c.192-150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 505,780 control chromosomes in the GnomAD database, including 17,514 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 0.29 (8387 hom., cov: 32)
  • Exomes 𝑓: 0.20 (9127 hom.)
• Consequence: PBX1 NM_002585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704

Genes affected

PBX1 (HGNC:8632): (PBX homeobox 1) This gene encodes a nuclear protein that belongs to the PBX homeobox family of transcriptional factors. Studies in mice suggest that this gene may be involved in the regulation of osteogenesis and required for skeletal patterning and programming. A chromosomal translocation, t(1;19) involving this gene and TCF3/E2A gene, is associated with pre-B-cell acute lymphoblastic leukemia. The resulting fusion protein, in which the DNA binding domain of E2A is replaced by the DNA binding domain of this protein, transforms cells by constitutively activating transcription of genes regulated by the PBX protein family. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX1	NM_002585.4	c.192-150T>C		intron_variant		ENST00000420696.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX1	ENST00000420696.7	c.192-150T>C		intron_variant		1	NM_002585.4	P4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43841 AN: 151794 Hom.: 8359 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.203 AC: 71894 AN: 353868 Hom.: 9127 AF XY: 0.200 AC XY: 37665 AN XY: 188552

Gnomad4 AFR exome AF: 0.521

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.289 AC: 43934 AN: 151912 Hom.: 8387 Cov.: 32 AF XY: 0.287 AC XY: 21272 AN XY: 74246

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.285

Alfa AF: 0.242 Hom.: 1918

Bravo AF: 0.311

Asia WGS AF: 0.364 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs4657364; hg19: chr1-164532325;