rs10918078

Positions:

• chr1-164842447-T-C

Variant summary

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

The NM_002585.4(PBX1):​c.1201-4137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,068 control chromosomes in the GnomAD database, including 11,030 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 (11030 hom., cov: 32)
• Consequence: PBX1 NM_002585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769

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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX1	NM_002585.4	c.1201-4137T>C		intron_variant		ENST00000420696.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX1	ENST00000420696.7	c.1201-4137T>C		intron_variant		1	NM_002585.4	P4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55810 AN: 151950 Hom.: 11001 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.368 AC: 55894 AN: 152068 Hom.: 11030 Cov.: 32 AF XY: 0.367 AC XY: 27281 AN XY: 74344

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.379

Alfa AF: 0.355 Hom.: 1499

Bravo AF: 0.365

Asia WGS AF: 0.312 AC: 1083 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.0
DANN	Benign	0.91

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: rs10918078; hg19: chr1-164811684;