rs2792248

chr1-164656025-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002585.4(PBX1):c.265+92714G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,070 control chromosomes in the GnomAD database, including 37,407 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 0.69 (37407 hom., cov: 32)
• Consequence: PBX1 NM_002585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX1	NM_002585.4	c.265+92714G>A		intron_variant		ENST00000420696.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX1	ENST00000420696.7	c.265+92714G>A		intron_variant		1	NM_002585.4	P4

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105469 AN: 151954 Hom.: 37403 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.694 AC: 105508 AN: 152070 Hom.: 37407 Cov.: 32 AF XY: 0.694 AC XY: 51559 AN XY: 74326

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.706

Alfa AF: 0.735 Hom.: 28599

Bravo AF: 0.678

Asia WGS AF: 0.664 AC: 2305 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	9.2
Dann	Benign	0.79

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: rs2792248; hg19: chr1-164625262;