rs10918078

Variant names:

• chr1-164842447-T-C
• rs10918078
• NM_002585.4:c.1201-4137T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: G2P, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002585.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX1	NM_002585.4	MANE Select	c.1201-4137T>C		intron	N/A	NP_002576.1	P40424-1
	PBX1	NM_001204963.2		c.1201-6893T>C		intron	N/A	NP_001191892.1	P40424-3
	PBX1	NM_001204961.2		c.*44-4137T>C		intron	N/A	NP_001191890.1	Q53YC7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX1	ENST00000420696.7	TSL:1 MANE Select	c.1201-4137T>C		intron	N/A	ENSP00000405890.2	P40424-1
	PBX1	ENST00000367897.5	TSL:1	c.*44-4137T>C		intron	N/A	ENSP00000356872.1	P40424-2
	PBX1	ENST00000540236.4	TSL:1	c.886-4137T>C		intron	N/A	ENSP00000439943.3	H0YLB0

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

African (AFR) AF: 0.504 AC: 20909 AN: 41474

American (AMR) AF: 0.275 AC: 4208 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1506 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1099 AN: 5168

South Asian (SAS) AF: 0.330 AC: 1589 AN: 4818

European-Finnish (FIN) AF: 0.346 AC: 3657 AN: 10572

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21624 AN: 67970

Other (OTH) AF: 0.379 AC: 802 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.0
DANN	Benign	0.91
PhyloP100		0.77
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: rs10918078; hg19: chr1-164811684;