rs760909

Variant names:

• chr6-170547792-A-C
• rs760909
• NM_002793.4:c.221+1214T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-170547792-A-C
• chr6-170547792-A-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.221+1214T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,440 control chromosomes in the GnomAD database, including 22,321 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 0.54 (22321 hom., cov: 29)
• Consequence: PSMB1 NM_002793.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 6 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: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB1	NM_002793.4	MANE Select	c.221+1214T>G		intron	N/A	NP_002784.1	A0A140VK45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB1	ENST00000262193.7	TSL:1 MANE Select	c.221+1214T>G		intron	N/A	ENSP00000262193.6	P20618
	PSMB1	ENST00000920418.1		c.221+1214T>G		intron	N/A	ENSP00000590477.1
	PSMB1	ENST00000892690.1		c.221+1214T>G		intron	N/A	ENSP00000562749.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81537 AN: 151322 Hom.: 22282 Cov.: 29

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.539 AC: 81623 AN: 151440 Hom.: 22321 Cov.: 29 AF XY: 0.537 AC XY: 39718 AN XY: 73950

African (AFR) AF: 0.614 AC: 25324 AN: 41236

American (AMR) AF: 0.468 AC: 7115 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3466

East Asian (EAS) AF: 0.786 AC: 4026 AN: 5122

South Asian (SAS) AF: 0.482 AC: 2317 AN: 4804

European-Finnish (FIN) AF: 0.486 AC: 5092 AN: 10474

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34125 AN: 67822

Other (OTH) AF: 0.536 AC: 1124 AN: 2098

Alfa AF: 0.522 Hom.: 8242

Bravo AF: 0.547

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		0.098
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: rs760909; hg19: chr6-170856880;