rs773121

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-56104457-G-A
• chr12-56104457-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PA2G4	NM_006191.3	c.-281G>A		upstream_gene_variant		ENST00000303305.11	NP_006182.2
LOC105369782	XR_944995.4	n.-38C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000257411	ENST00000548861.2	c.32-2131G>A		intron_variant	Intron 1 of 5	5		ENSP00000449770.3
PA2G4	ENST00000303305.11	c.-281G>A		upstream_gene_variant		1	NM_006191.3	ENSP00000302886.6
PA2G4	ENST00000552766.5	c.-281G>A		upstream_gene_variant		5		ENSP00000448557.1
ENSG00000257553	ENST00000548595.1	n.*157C>T		downstream_gene_variant		5

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

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0601

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.000387

Gnomad4 SAS exome AF: 0.0788

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.103

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

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.108 Hom.: 905

Bravo AF: 0.114

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.82

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: rs773121; hg19: chr12-56498241;