12-56104457-G-A

Variant names:

• chr12-56104457-G-A
• rs773121
• ENST00000548861.2:c.32-2131G>A

Variant summary

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

The ENST00000548861.2(ENSG00000257411):​c.32-2131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 656,956 control chromosomes in the GnomAD database, including 3,852 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 0.12 (1138 hom., cov: 32)
  • Exomes 𝑓: 0.097 (2714 hom.)
• Consequence: ENSG00000257411 ENST00000548861.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 16 publications found

Genes affected

ENSG00000257411 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000548861.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PA2G4	NM_006191.3	MANE Select	c.-281G>A		upstream_gene	N/A	NP_006182.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000257411	ENST00000548861.2	TSL:5	c.32-2131G>A		intron	N/A	ENSP00000449770.3
	PA2G4	ENST00000303305.11	TSL:1 MANE Select	c.-281G>A		upstream_gene	N/A	ENSP00000302886.6
	PA2G4	ENST00000552766.5	TSL:5	c.-281G>A		upstream_gene	N/A	ENSP00000448557.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17602 AN: 152118 Hom.: 1133 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0966

GnomAD4 exome AF: 0.0972 AC: 49082 AN: 504720 Hom.: 2714 Cov.: 0 AF XY: 0.0961 AC XY: 26354 AN XY: 274300

African (AFR) AF: 0.158 AC: 2346 AN: 14838

American (AMR) AF: 0.0601 AC: 1988 AN: 33080

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 1997 AN: 18598

East Asian (EAS) AF: 0.000387 AC: 11 AN: 28450

South Asian (SAS) AF: 0.0788 AC: 4837 AN: 61400

European-Finnish (FIN) AF: 0.118 AC: 3582 AN: 30354

Middle Eastern (MID) AF: 0.0784 AC: 268 AN: 3418

European-Non Finnish (NFE) AF: 0.109 AC: 31201 AN: 286838

Other (OTH) AF: 0.103 AC: 2852 AN: 27744

GnomAD4 genome AF: 0.116 AC: 17621 AN: 152236 Hom.: 1138 Cov.: 32 AF XY: 0.115 AC XY: 8571 AN XY: 74442

African (AFR) AF: 0.157 AC: 6524 AN: 41536

American (AMR) AF: 0.0879 AC: 1345 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4832

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7418 AN: 67982

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.109 Hom.: 1202

Bravo AF: 0.114

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		1.0
PromoterAI		0.0077	Neutral
Mutation Taster		=300/0	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: rs773121; hg19: chr12-56498241;