12-56104119-C-T

Variant names:

• chr12-56104119-C-T
• rs3759094
• ENST00000548861.2:c.32-2469C>T

Variant summary

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

The ENST00000548861.2(ENSG00000257411):​c.32-2469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,978 control chromosomes in the GnomAD database, including 6,655 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 0.29 (6655 hom., cov: 31)
• Consequence: ENSG00000257411 ENST00000548861.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 10 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 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

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
	ENSG00000257411	ENST00000548861.2	TSL:5	c.32-2469C>T		intron	N/A	ENSP00000449770.3	H0YIN7
	ENSG00000295820	ENST00000732893.1		n.288G>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000295820	ENST00000732894.1		n.106+169G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43516 AN: 151860 Hom.: 6642 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.287 AC: 43563 AN: 151978 Hom.: 6655 Cov.: 31 AF XY: 0.286 AC XY: 21207 AN XY: 74270

African (AFR) AF: 0.172 AC: 7116 AN: 41462

American (AMR) AF: 0.303 AC: 4634 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3470

East Asian (EAS) AF: 0.342 AC: 1765 AN: 5160

South Asian (SAS) AF: 0.271 AC: 1300 AN: 4804

European-Finnish (FIN) AF: 0.321 AC: 3398 AN: 10570

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22849 AN: 67916

Other (OTH) AF: 0.315 AC: 664 AN: 2110

Alfa AF: 0.283 Hom.: 1824

Bravo AF: 0.284

Asia WGS AF: 0.321 AC: 1118 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		1.2
PromoterAI		-0.012	Neutral

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: rs3759094; hg19: chr12-56497903;