6-170552941-G-T

Variant names:

• chr6-170552941-G-T
• rs12210583
• NM_002793.4:c.113+189C>A

Variant summary

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

The NM_002793.4(PSMB1):​c.113+189C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,304 control chromosomes in the GnomAD database, including 396 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 0.064 (396 hom., cov: 34)
• Consequence: PSMB1 NM_002793.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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.113+189C>A		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.113+189C>A		intron	N/A	ENSP00000262193.6	P20618
	PSMB1	ENST00000920418.1		c.113+189C>A		intron	N/A	ENSP00000590477.1
	PSMB1	ENST00000892690.1		c.113+189C>A		intron	N/A	ENSP00000562749.1

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9786 AN: 152186 Hom.: 396 Cov.: 34

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0643 AC: 9788 AN: 152304 Hom.: 396 Cov.: 34 AF XY: 0.0617 AC XY: 4593 AN XY: 74474

African (AFR) AF: 0.106 AC: 4389 AN: 41570

American (AMR) AF: 0.0568 AC: 869 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4832

European-Finnish (FIN) AF: 0.0333 AC: 353 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0555 AC: 3773 AN: 68026

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0408 Hom.: 44

Bravo AF: 0.0671

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.74
PhyloP100		-0.71
PromoterAI		-0.045	Neutral
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: rs12210583; hg19: chr6-170862029;