rs2792248

Variant names:

• chr1-164656025-G-A
• rs2792248
• NM_002585.4:c.265+92714G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

PBX1 Gene-Disease associations (from GenCC):

• congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Illumina, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PBX1	NM_002585.4	c.265+92714G>A		intron_variant	Intron 2 of 8	ENST00000420696.7	NP_002576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX1	ENST00000420696.7	c.265+92714G>A		intron_variant	Intron 2 of 8	1	NM_002585.4	ENSP00000405890.2

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

African (AFR) AF: 0.546 AC: 22646 AN: 41444

American (AMR) AF: 0.714 AC: 10912 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3549 AN: 5158

South Asian (SAS) AF: 0.674 AC: 3251 AN: 4822

European-Finnish (FIN) AF: 0.805 AC: 8530 AN: 10594

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51963 AN: 67986

Other (OTH) AF: 0.706 AC: 1490 AN: 2110

Alfa AF: 0.733 Hom.: 33763

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
PhyloP100		-0.080
Mutation Taster		=100/0	polymorphism (auto)

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: rs2792248; hg19: chr1-164625262;