NM_002793.4:c.114-319T>G

Variant names:

• chr6-170549432-A-C
• rs6914744
• NM_002793.4:c.114-319T>G

Variant summary

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

The NM_002793.4(PSMB1):​c.114-319T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 228,022 control chromosomes in the GnomAD database, including 23,709 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 0.44 (15083 hom., cov: 33)
  • Exomes 𝑓: 0.46 (8626 hom.)
• Consequence: PSMB1 NM_002793.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 3 publications found

Genes affected

PSMB1 (HGNC:9537): (proteasome 20S subunit beta 1) 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. This gene is tightly linked to the TBP (TATA-binding protein) gene in human and in mouse, and is transcribed in the opposite orientation in both species. [provided by RefSeq, Jul 2008]

PSMB1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, hypotonia, and absent language

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

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 = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002793.4. 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
	PSMB1	NM_002793.4	MANE Select	c.114-319T>G		intron	N/A	NP_002784.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB1	ENST00000262193.7	TSL:1 MANE Select	c.114-319T>G		intron	N/A	ENSP00000262193.6
	PSMB1	ENST00000462957.1	TSL:2	n.1010T>G		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66590 AN: 151910 Hom.: 15059 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.463 AC: 35172 AN: 75994 Hom.: 8626 Cov.: 0 AF XY: 0.464 AC XY: 18131 AN XY: 39102

African (AFR) AF: 0.378 AC: 937 AN: 2482

American (AMR) AF: 0.428 AC: 1711 AN: 3994

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1108 AN: 2752

East Asian (EAS) AF: 0.781 AC: 4165 AN: 5336

South Asian (SAS) AF: 0.399 AC: 2076 AN: 5208

European-Finnish (FIN) AF: 0.448 AC: 1222 AN: 2728

Middle Eastern (MID) AF: 0.388 AC: 132 AN: 340

European-Non Finnish (NFE) AF: 0.449 AC: 21727 AN: 48402

Other (OTH) AF: 0.441 AC: 2094 AN: 4752

GnomAD4 genome AF: 0.438 AC: 66658 AN: 152028 Hom.: 15083 Cov.: 33 AF XY: 0.441 AC XY: 32754 AN XY: 74324

African (AFR) AF: 0.367 AC: 15224 AN: 41446

American (AMR) AF: 0.418 AC: 6395 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1347 AN: 3462

East Asian (EAS) AF: 0.773 AC: 3998 AN: 5174

South Asian (SAS) AF: 0.421 AC: 2033 AN: 4826

European-Finnish (FIN) AF: 0.471 AC: 4979 AN: 10564

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31051 AN: 67954

Other (OTH) AF: 0.447 AC: 945 AN: 2114

Alfa AF: 0.448 Hom.: 3778

Bravo AF: 0.438

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		-0.42
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: rs6914744; hg19: chr6-170858520;