chr1-164594188-A-G

Variant names:

• chr1-164594188-A-G
• rs2800791
• NM_002585.4:c.265+30877A>G

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+30877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,118 control chromosomes in the GnomAD database, including 12,255 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 0.40 (12255 hom., cov: 34)
• Consequence: PBX1 NM_002585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX1	NM_002585.4	c.265+30877A>G		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+30877A>G		intron_variant	Intron 2 of 8	1	NM_002585.4	ENSP00000405890.2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60495 AN: 152000 Hom.: 12252 Cov.: 34

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.398 AC: 60518 AN: 152118 Hom.: 12255 Cov.: 34 AF XY: 0.401 AC XY: 29800 AN XY: 74352

African (AFR) AF: 0.313 AC: 13003 AN: 41508

American (AMR) AF: 0.419 AC: 6403 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1306 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2651 AN: 5160

South Asian (SAS) AF: 0.455 AC: 2194 AN: 4822

European-Finnish (FIN) AF: 0.460 AC: 4864 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28759 AN: 67982

Other (OTH) AF: 0.420 AC: 888 AN: 2112

Alfa AF: 0.414 Hom.: 9977

Bravo AF: 0.388

Asia WGS AF: 0.498 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.59
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2800791; hg19: chr1-164563425;