rs12610185

chr19-19610913-G-A

Variant summary

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

The NM_025245.3(PBX4):c.119+7598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 152,198 control chromosomes in the GnomAD database, including 621 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 0.087 (621 hom., cov: 32)
• Consequence: PBX4 NM_025245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

Genes affected

PBX4 (HGNC:13403): (PBX homeobox 4) This gene encodes a member of the pre-B cell leukemia transcription factor family. These proteins are homeobox proteins that play critical roles in embryonic development and cellular differentiation both as Hox cofactors and through Hox-independent pathways. The encoded protein contains a homeobox DNA-binding domain, but specific functions of the protein have not been determined. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX4	NM_025245.3	c.119+7598C>T		intron_variant		ENST00000251203.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX4	ENST00000251203.14	c.119+7598C>T		intron_variant		1	NM_025245.3	P1
PBX4	ENST00000557978.6	c.119+7598C>T		intron_variant, NMD_transcript_variant		1
PBX4	ENST00000558222.1	c.119+7598C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13252 AN: 152080 Hom.: 612 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0601

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.0759

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

GnomAD4 genome AF: 0.0873 AC: 13285 AN: 152198 Hom.: 621 Cov.: 32 AF XY: 0.0882 AC XY: 6564 AN XY: 74406

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.0989

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0601

Gnomad4 NFE AF: 0.0801

Gnomad4 OTH AF: 0.0846

Alfa AF: 0.0831 Hom.: 364

Bravo AF: 0.0866

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.67

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: rs12610185; hg19: chr19-19721722;