rs2292117

chr15-78542347-A-Gchr15-78542347-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002789.6(PSMA4):c.46+128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,375,646 control chromosomes in the GnomAD database, including 260,989 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 0.67 (34696 hom., cov: 33)
  • Exomes 𝑓: 0.60 (226293 hom.)
• Consequence: PSMA4 NM_002789.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

Genes affected

PSMA4 (HGNC:9533): (proteasome 20S subunit alpha 4) This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA4	NM_002789.6	c.46+128A>G		intron_variant		ENST00000044462.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMA4	ENST00000044462.12	c.46+128A>G		intron_variant		1	NM_002789.6	P1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101565 AN: 152046 Hom.: 34653 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.676

GnomAD4 exome AF: 0.602 AC: 736505 AN: 1223482 Hom.: 226293 Cov.: 17 AF XY: 0.603 AC XY: 369306 AN XY: 612298

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.652

Gnomad4 EAS exome AF: 0.877

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.668 AC: 101668 AN: 152164 Hom.: 34696 Cov.: 33 AF XY: 0.672 AC XY: 50005 AN XY: 74358

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.675

Alfa AF: 0.610 Hom.: 13672

Bravo AF: 0.681

Asia WGS AF: 0.732 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.39

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: rs2292117; hg19: chr15-78834689;