rs1387389

Variant names:

• chr1-164720525-G-A
• rs1387389
• NM_002585.4:c.266-71969G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-164720525-G-A
• chr1-164720525-G-C
• chr1-164720525-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002585.4(PBX1):​c.266-71969G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,960 control chromosomes in the GnomAD database, including 10,612 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 0.36 (10612 hom., cov: 32)
• Consequence: PBX1 NM_002585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 19 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX1	NM_002585.4	c.266-71969G>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.266-71969G>A		intron_variant	Intron 2 of 8	1	NM_002585.4	ENSP00000405890.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55179 AN: 151842 Hom.: 10597 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.363 AC: 55210 AN: 151960 Hom.: 10612 Cov.: 32 AF XY: 0.365 AC XY: 27123 AN XY: 74236

African (AFR) AF: 0.435 AC: 18027 AN: 41430

American (AMR) AF: 0.284 AC: 4339 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.568 AC: 2922 AN: 5146

South Asian (SAS) AF: 0.529 AC: 2549 AN: 4820

European-Finnish (FIN) AF: 0.296 AC: 3128 AN: 10558

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22146 AN: 67948

Other (OTH) AF: 0.332 AC: 702 AN: 2112

Alfa AF: 0.354 Hom.: 7419

Bravo AF: 0.365

Asia WGS AF: 0.507 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		0.097
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: rs1387389; hg19: chr1-164689762;