12-56114625-G-C

Variant names:

• chr12-56114625-G-C
• rs4759228
• ENST00000870200.1:c.*2-1173G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000870200.1(PA2G4):​c.*2-1173G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,078 control chromosomes in the GnomAD database, including 3,946 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 0.21 (3946 hom., cov: 31)
• Consequence: PA2G4 ENST00000870200.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 20 publications found

Genes affected

PA2G4 (HGNC:8550): (proliferation-associated 2G4) This gene encodes an RNA-binding protein that is involved in growth regulation. This protein is present in pre-ribosomal ribonucleoprotein complexes and may be involved in ribosome assembly and the regulation of intermediate and late steps of rRNA processing. This protein can interact with the cytoplasmic domain of the ErbB3 receptor and may contribute to transducing growth regulatory signals. This protein is also a transcriptional co-repressor of androgen receptor-regulated genes and other cell cycle regulatory genes through its interactions with histone deacetylases. This protein has been implicated in growth inhibition and the induction of differentiation of human cancer cells. Six pseudogenes, located on chromosomes 3, 6, 9, 18, 20 and X, have been identified. [provided by RefSeq, Jul 2008]

ENSG00000258317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000870200.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PA2G4	ENST00000870200.1		c.*2-1173G>C		intron	N/A	ENSP00000540259.1
	ENSG00000258317	ENST00000716007.1		n.756+1873C>G		intron	N/A
	ENSG00000258317	ENST00000732776.1		n.905+1873C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32053 AN: 151960 Hom.: 3945 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.211 AC: 32066 AN: 152078 Hom.: 3946 Cov.: 31 AF XY: 0.206 AC XY: 15304 AN XY: 74338

African (AFR) AF: 0.103 AC: 4251 AN: 41472

American (AMR) AF: 0.187 AC: 2856 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.0714 AC: 370 AN: 5182

South Asian (SAS) AF: 0.180 AC: 867 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2367 AN: 10580

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19409 AN: 67970

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.244 Hom.: 592

Bravo AF: 0.205

Asia WGS AF: 0.118 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.63
PhyloP100		-0.044

Splicing

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

Other links and lift over

dbSNP: rs4759228; hg19: chr12-56508409;