rs2292117

Variant names:

• chr15-78542347-A-G
• rs2292117
• NM_002789.6:c.46+128A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78542347-A-G
• chr15-78542347-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002789.6. 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
	PSMA4	NM_002789.6	MANE Select	c.46+128A>G		intron	N/A	NP_002780.1	P25789-1
	PSMA4	NM_001102667.2		c.46+128A>G		intron	N/A	NP_001096137.1	P25789-1
	PSMA4	NM_001330676.2		c.46+128A>G		intron	N/A	NP_001317605.1	P25789-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA4	ENST00000044462.12	TSL:1 MANE Select	c.46+128A>G		intron	N/A	ENSP00000044462.7	P25789-1
	PSMA4	ENST00000413382.6	TSL:1	c.-5+128A>G		intron	N/A	ENSP00000402118.2	P25789-2
	PSMA4	ENST00000558635.1	TSL:1	n.524A>G		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.789 AC: 21250 AN: 26922

American (AMR) AF: 0.789 AC: 23080 AN: 29256

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 13284 AN: 20368

East Asian (EAS) AF: 0.877 AC: 33657 AN: 38384

South Asian (SAS) AF: 0.673 AC: 46520 AN: 69122

European-Finnish (FIN) AF: 0.628 AC: 31770 AN: 50556

Middle Eastern (MID) AF: 0.722 AC: 3644 AN: 5050

European-Non Finnish (NFE) AF: 0.570 AC: 530978 AN: 932134

Other (OTH) AF: 0.625 AC: 32322 AN: 51690

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

African (AFR) AF: 0.780 AC: 32379 AN: 41532

American (AMR) AF: 0.746 AC: 11405 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2244 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4327 AN: 5170

South Asian (SAS) AF: 0.668 AC: 3220 AN: 4822

European-Finnish (FIN) AF: 0.624 AC: 6601 AN: 10574

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39318 AN: 67990

Other (OTH) AF: 0.675 AC: 1424 AN: 2110

Alfa AF: 0.608 Hom.: 15009

Bravo AF: 0.681

Asia WGS AF: 0.732 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.69
Mutation Taster		=100/0	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: rs2292117; hg19: chr15-78834689;