1-164792478-C-CTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002585.4(PBX1):c.266-15_266-14insTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0063 in 1,613,508 control chromosomes in the GnomAD database, including 553 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (297 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (256 hom.)
• Consequence: PBX1 NM_002585.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0360

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 -16 ACMG points.

• BP6: Variant 1-164792478-C-CTT is Benign according to our data. Variant chr1-164792478-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1599700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX1	NM_002585.4	c.266-15_266-14insTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000420696.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX1	ENST00000420696.7	c.266-15_266-14insTT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002585.4	P4

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5012 AN: 152116 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0173

GnomAD3 exomes AF: 0.00853 AC: 2119 AN: 248316 Hom.: 98 AF XY: 0.00618 AC XY: 831 AN XY: 134550

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.00519

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.00591

GnomAD4 exome AF: 0.00352 AC: 5137 AN: 1461274 Hom.: 256 Cov.: 32 AF XY: 0.00300 AC XY: 2180 AN XY: 726926

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.00640

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.00756

GnomAD4 genome AF: 0.0330 AC: 5027 AN: 152234 Hom.: 297 Cov.: 32 AF XY: 0.0315 AC XY: 2342 AN XY: 74436

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0151 Hom.: 25

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139680846; hg19: chr1-164761715;