rs12610185

Variant names:

• chr19-19610913-G-A
• rs12610185
• NM_025245.3:c.119+7598C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PBX4	NM_025245.3	c.119+7598C>T		intron_variant	Intron 1 of 7	ENST00000251203.14	NP_079521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX4	ENST00000251203.14	c.119+7598C>T		intron_variant	Intron 1 of 7	1	NM_025245.3	ENSP00000251203.5
PBX4	ENST00000557978.6	n.119+7598C>T		intron_variant	Intron 1 of 7	1		ENSP00000453348.1
PBX4	ENST00000558222.1	n.119+7598C>T		intron_variant	Intron 1 of 5	2		ENSP00000453069.1

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

African (AFR) AF: 0.106 AC: 4390 AN: 41516

American (AMR) AF: 0.0707 AC: 1079 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3472

East Asian (EAS) AF: 0.0989 AC: 513 AN: 5186

South Asian (SAS) AF: 0.151 AC: 725 AN: 4812

European-Finnish (FIN) AF: 0.0601 AC: 637 AN: 10606

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0801 AC: 5451 AN: 68022

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.0842 Hom.: 1211

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
PhyloP100		0.16
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: rs12610185; hg19: chr19-19721722;