rs6074191

Variant names:

• chr20-1155512-C-A
• rs6074191
• NM_006814.5:c.552-7618C>A

Variant summary

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

The NM_006814.5(PSMF1):​c.552-7618C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,990 control chromosomes in the GnomAD database, including 13,749 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 0.42 (13749 hom., cov: 32)
• Consequence: PSMF1 NM_006814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMF1	NM_006814.5	c.552-7618C>A		intron_variant	Intron 4 of 6	ENST00000335877.11	NP_006805.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMF1	ENST00000335877.11	c.552-7618C>A		intron_variant	Intron 4 of 6	1	NM_006814.5	ENSP00000338039.6

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63745 AN: 151872 Hom.: 13731 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.420 AC: 63803 AN: 151990 Hom.: 13749 Cov.: 32 AF XY: 0.423 AC XY: 31439 AN XY: 74278

African (AFR) AF: 0.453 AC: 18762 AN: 41432

American (AMR) AF: 0.410 AC: 6270 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1473 AN: 3472

East Asian (EAS) AF: 0.705 AC: 3646 AN: 5170

South Asian (SAS) AF: 0.460 AC: 2214 AN: 4816

European-Finnish (FIN) AF: 0.392 AC: 4135 AN: 10540

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.383 AC: 26030 AN: 67968

Other (OTH) AF: 0.425 AC: 894 AN: 2106

Alfa AF: 0.398 Hom.: 15053

Bravo AF: 0.420

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.76
PhyloP100		-1.2
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: rs6074191; hg19: chr20-1136156;