rs1984001

Positions:

• chr9-124375522-T-C
• chr9-124375522-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002799.4(PSMB7):​c.570+9076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,776 control chromosomes in the GnomAD database, including 18,615 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 0.49 (18615 hom., cov: 30)
• Consequence: PSMB7 NM_002799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

Genes affected

PSMB7 (HGNC:9544): (proteasome 20S subunit beta 7) 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. The encoded protein is a member of the proteasome B-type family, also known as the T1B family, and is a 20S core beta subunit in the proteasome. Expression of this catalytic subunit is downregulated by gamma interferon, and proteolytic processing is required to generate a mature subunit. A pseudogene of this gene is located on the long arm of chromosome 14. [provided by RefSeq, Jul 2012]

PSMB7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMB7	NM_002799.4	c.570+9076A>G		intron_variant		ENST00000259457.8	NP_002790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMB7	ENST00000259457.8	c.570+9076A>G		intron_variant		1	NM_002799.4	ENSP00000259457.3
PSMB7	ENST00000498485.5	n.571+9076A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73817 AN: 151654 Hom.: 18610 Cov.: 30

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.487 AC: 73844 AN: 151776 Hom.: 18615 Cov.: 30 AF XY: 0.482 AC XY: 35742 AN XY: 74192

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.511

Alfa AF: 0.424 Hom.: 1335

Bravo AF: 0.475

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs1984001; hg19: chr9-127137801;