1-164769934-T-C

Variant names:

• chr1-164769934-T-C
• rs6670655
• NM_002585.4:c.266-22560T>C

Variant summary

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

The NM_002585.4(PBX1):​c.266-22560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 151,982 control chromosomes in the GnomAD database, including 38,866 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 0.71 (38863 hom., cov: 31)
  • Exomes 𝑓: 0.71 (3 hom.)
• Consequence: PBX1 NM_002585.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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-AS1 (HGNC:40425): (PBX1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX1	NM_002585.4	c.266-22560T>C		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.266-22560T>C		intron_variant	Intron 2 of 8	1	NM_002585.4	ENSP00000405890.2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107857 AN: 151850 Hom.: 38832 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.712

GnomAD4 exome AF: 0.714 AC: 10 AN: 14 Hom.: 3 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.710 AC: 107937 AN: 151968 Hom.: 38863 Cov.: 31 AF XY: 0.710 AC XY: 52761 AN XY: 74280

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.712

Alfa AF: 0.751 Hom.: 92977

Bravo AF: 0.691

Asia WGS AF: 0.775 AC: 2696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.73

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: rs6670655; hg19: chr1-164739171;