rs7172

Variant names:

• chr1-151399662-G-A
• rs7172
• NM_002796.3:c.75G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151399662-G-A
• chr1-151399662-G-C
• chr1-151399662-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002796.3(PSMB4):​c.75G>A​(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,613,768 control chromosomes in the GnomAD database, including 485,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (34866 hom., cov: 31)
  • Exomes 𝑓: 0.77 (450308 hom.)
• Consequence: PSMB4 NM_002796.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0750
• Publications: 38 publications found

Genes affected

PSMB4 (HGNC:9541): (proteasome 20S subunit beta 4) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. [provided by RefSeq, Jul 2008]

PSMB4 Gene-Disease associations (from GenCC):

• proteasome-associated autoinflammatory syndrome 3

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000307595 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-151399662-G-A is Benign according to our data. Variant chr1-151399662-G-A is described in ClinVar as Benign. ClinVar VariationId is 1165733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.075 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002796.3. 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
	PSMB4	NM_002796.3	MANE Select	c.75G>A	p.Pro25Pro	synonymous	Exon 1 of 7	NP_002787.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB4	ENST00000290541.7	TSL:1 MANE Select	c.75G>A	p.Pro25Pro	synonymous	Exon 1 of 7	ENSP00000290541.6	P28070
	PSMB4	ENST00000933662.1		c.75G>A	p.Pro25Pro	synonymous	Exon 1 of 6	ENSP00000603721.1
	PSMB4	ENST00000933663.1		c.75G>A	p.Pro25Pro	synonymous	Exon 1 of 6	ENSP00000603722.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97600 AN: 151854 Hom.: 34862 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.682

GnomAD2 exomes AF: 0.665 AC: 167147 AN: 251210 AF XY: 0.688

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.397

Gnomad ASJ exome AF: 0.791

Gnomad EAS exome AF: 0.221

Gnomad FIN exome AF: 0.773

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.725

GnomAD4 exome AF: 0.771 AC: 1127646 AN: 1461796 Hom.: 450308 Cov.: 63 AF XY: 0.772 AC XY: 561664 AN XY: 727202

African (AFR) AF: 0.363 AC: 12165 AN: 33474

American (AMR) AF: 0.415 AC: 18547 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 20790 AN: 26136

East Asian (EAS) AF: 0.210 AC: 8348 AN: 39694

South Asian (SAS) AF: 0.692 AC: 59680 AN: 86242

European-Finnish (FIN) AF: 0.776 AC: 41444 AN: 53420

Middle Eastern (MID) AF: 0.781 AC: 4496 AN: 5758

European-Non Finnish (NFE) AF: 0.825 AC: 917208 AN: 1111978

Other (OTH) AF: 0.745 AC: 44968 AN: 60392

GnomAD4 genome AF: 0.642 AC: 97624 AN: 151972 Hom.: 34866 Cov.: 31 AF XY: 0.638 AC XY: 47360 AN XY: 74288

African (AFR) AF: 0.374 AC: 15499 AN: 41434

American (AMR) AF: 0.558 AC: 8514 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2785 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1087 AN: 5132

South Asian (SAS) AF: 0.679 AC: 3272 AN: 4818

European-Finnish (FIN) AF: 0.766 AC: 8088 AN: 10560

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55867 AN: 67968

Other (OTH) AF: 0.684 AC: 1444 AN: 2112

Alfa AF: 0.741 Hom.: 135213

Bravo AF: 0.608

Asia WGS AF: 0.507 AC: 1764 AN: 3478

EpiCase AF: 0.817

EpiControl AF: 0.819

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Proteasome-associated autoinflammatory syndrome 3 (1)
-	-	1	PSMB4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.0
DANN	Benign	0.89
PhyloP100		-0.075
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs7172; hg19: chr1-151372138; COSMIC: COSV51850826; COSMIC: COSV51850826;