rs11580794

chr1-164887535-A-G

Variant summary

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

The ENST00000558796.2(PBX1):n.258-11653A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 152,302 control chromosomes in the GnomAD database, including 257 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 0.044 (257 hom., cov: 32)
• Consequence: PBX1 ENST00000558796.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX1	ENST00000558796.2	n.258-11653A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6771 AN: 152184 Hom.: 257 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0444 AC: 6769 AN: 152302 Hom.: 257 Cov.: 32 AF XY: 0.0436 AC XY: 3250 AN XY: 74458

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.0799

Gnomad4 NFE AF: 0.0682

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0603 Hom.: 167

Bravo AF: 0.0406

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11580794; hg19: chr1-164856772;