rs12723035

Positions:

• chr1-164850925-A-G

Variant summary

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

The NM_002585.4(PBX1):​c.*4249A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 211,450 control chromosomes in the GnomAD database, including 14,680 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 0.37 (11103 hom., cov: 32)
  • Exomes 𝑓: 0.34 (3577 hom.)
• Consequence: PBX1 NM_002585.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBX1	NM_002585.4	c.*4249A>G		3_prime_UTR_variant	9/9	ENST00000420696.7	NP_002576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBX1	ENST00000420696.7	c.*4249A>G		3_prime_UTR_variant	9/9	1	NM_002585.4	ENSP00000405890	P4
PBX1	ENST00000699845.1	c.*43+29299A>G		intron_variant				ENSP00000514643	A1
PBX1	ENST00000699848.1	c.758+29299A>G		intron_variant				ENSP00000514646
PBX1	ENST00000558796.2	n.257+19442A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56365 AN: 151870 Hom.: 11073 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.337 AC: 20009 AN: 59462 Hom.: 3577 Cov.: 0 AF XY: 0.340 AC XY: 9343 AN XY: 27478

Gnomad4 AFR exome AF: 0.497

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.371 AC: 56447 AN: 151988 Hom.: 11103 Cov.: 32 AF XY: 0.371 AC XY: 27551 AN XY: 74288

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.383

Alfa AF: 0.342 Hom.: 2491

Bravo AF: 0.367

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.36

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: rs12723035; hg19: chr1-164820162;