rs2307840

Variant names:

• chr1-35633487-AAC-A
• rs2307840
• NM_002794.5:c.215-2145_215-2144delGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002794.5(PSMB2):​c.215-2145_215-2144delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (47262 hom., cov: 0)
• Consequence: PSMB2 NM_002794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 5 publications found

Genes affected

PSMB2 (HGNC:9539): (proteasome 20S subunit beta 2) 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. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB2	NM_002794.5	c.215-2145_215-2144delGT		intron_variant	Intron 2 of 5	ENST00000373237.4	NP_002785.1
PSMB2	NM_001199779.2	c.140-2145_140-2144delGT		intron_variant	Intron 2 of 5		NP_001186708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB2	ENST00000373237.4	c.215-2145_215-2144delGT		intron_variant	Intron 2 of 5	1	NM_002794.5	ENSP00000362334.3

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112442 AN: 151876 Hom.: 47265 Cov.: 0

Gnomad AFR AF: 0.379

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.740 AC: 112448 AN: 151994 Hom.: 47262 Cov.: 0 AF XY: 0.734 AC XY: 54507 AN XY: 74296

African (AFR) AF: 0.379 AC: 15695 AN: 41418

American (AMR) AF: 0.683 AC: 10435 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3315 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1153 AN: 5170

South Asian (SAS) AF: 0.746 AC: 3596 AN: 4822

European-Finnish (FIN) AF: 0.906 AC: 9560 AN: 10550

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65883 AN: 67970

Other (OTH) AF: 0.772 AC: 1631 AN: 2112

Alfa AF: 0.846 Hom.: 7121

Bravo AF: 0.705

Asia WGS AF: 0.490 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
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: rs2307840; hg19: chr1-36099088;