dbSNP rs6914744: PSMB1:c.114-319T>G (chr6-170549432-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.425

Publications

3 publications found

Variant links:

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

PSMB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB1	NM_002793.4 link	c.114-319T>G		intron_variant	Intron 1 of 5	ENST00000262193.7	NP_002784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB1	ENST00000262193.7 link	c.114-319T>G		intron_variant	Intron 1 of 5	1	NM_002793.4	ENSP00000262193.6
PSMB1	ENST00000462957.1 link	n.1010T>G		non_coding_transcript_exon_variant	Exon 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66590

AN:

151910

Hom.:

15059

Cov.:

show subpopulations

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.:

AF XY:

0.464

AC XY:

18131

AN XY:

39102

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

912

1824

2736

3648

4560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.438

AC:

66658

AN:

152028

Hom.:

15083

Cov.:

AF XY:

0.441

AC XY:

32754

AN XY:

74324

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1893

3785

5678

7570

9463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.34

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over