rs4813030

Variant names:

• chr20-1116966-T-C
• rs4813030
• ENST00000333082.7:c.-21-1787T>C

Variant summary

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

The NM_178578.4(PSMF1):​c.-21-1787T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,998 control chromosomes in the GnomAD database, including 42,889 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 0.74 (42889 hom., cov: 32)
• Consequence: PSMF1 NM_178578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 9 publications found

Genes affected

PSMF1 (HGNC:9571): (proteasome inhibitor subunit 1) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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 protein that inhibits the activation of the proteasome by the 11S and 19S regulators. Alternative transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

ENSG00000286787 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178578.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	NM_178578.4		c.-21-1787T>C		intron	N/A	NP_848693.2
	PSMF1	NM_001323407.2		c.-136+3557T>C		intron	N/A	NP_001310336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	ENST00000333082.7	TSL:1	c.-21-1787T>C		intron	N/A	ENSP00000327704.3
	PSMF1	ENST00000381899.8	TSL:2	c.-21-1787T>C		intron	N/A	ENSP00000371324.4
	PSMF1	ENST00000479715.5	TSL:3	n.104+3557T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111984 AN: 151880 Hom.: 42888 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.737 AC: 112015 AN: 151998 Hom.: 42889 Cov.: 32 AF XY: 0.744 AC XY: 55260 AN XY: 74314

African (AFR) AF: 0.505 AC: 20885 AN: 41358

American (AMR) AF: 0.823 AC: 12586 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3472

East Asian (EAS) AF: 0.938 AC: 4857 AN: 5176

South Asian (SAS) AF: 0.917 AC: 4425 AN: 4824

European-Finnish (FIN) AF: 0.821 AC: 8697 AN: 10588

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54764 AN: 67974

Other (OTH) AF: 0.773 AC: 1629 AN: 2108

Alfa AF: 0.797 Hom.: 81801

Bravo AF: 0.727

Asia WGS AF: 0.866 AC: 3012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.38
PhyloP100		0.036
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: rs4813030; hg19: chr20-1097609;