chr2-231160570-G-A

Variant names:

• chr2-231160570-G-A
• rs6437002
• NM_002807.4:c.2219-770G>A

Variant summary

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

The NM_002807.4(PSMD1):​c.2219-770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,202 control chromosomes in the GnomAD database, including 45,851 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 0.77 (45851 hom., cov: 32)
• Consequence: PSMD1 NM_002807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 8 publications found

Genes affected

PSMD1 (HGNC:9554): (proteasome 26S subunit, non-ATPase 1) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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 the largest non-ATPase subunit of the 19S regulator lid, which is responsible for substrate recognition and binding. There is evidence that this proteasome and its subunits interact with viral proteins, including those of coronaviruses. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Aug 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002807.4. 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
	PSMD1	NM_002807.4	MANE Select	c.2219-770G>A		intron	N/A	NP_002798.2
	PSMD1	NM_001191037.2		c.2219-770G>A		intron	N/A	NP_001177966.1
	PSMD1	NR_034059.2		n.2208-770G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD1	ENST00000308696.11	TSL:1 MANE Select	c.2219-770G>A		intron	N/A	ENSP00000309474.6
	PSMD1	ENST00000431051.6	TSL:1	n.*1902-770G>A		intron	N/A	ENSP00000400483.1
	PSMD1	ENST00000677230.1		c.2219-770G>A		intron	N/A	ENSP00000503068.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116894 AN: 152084 Hom.: 45798 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.769 AC: 117002 AN: 152202 Hom.: 45851 Cov.: 32 AF XY: 0.774 AC XY: 57553 AN XY: 74398

African (AFR) AF: 0.928 AC: 38577 AN: 41552

American (AMR) AF: 0.761 AC: 11641 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2284 AN: 3470

East Asian (EAS) AF: 0.836 AC: 4337 AN: 5188

South Asian (SAS) AF: 0.714 AC: 3444 AN: 4822

European-Finnish (FIN) AF: 0.795 AC: 8403 AN: 10576

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 46035 AN: 67990

Other (OTH) AF: 0.730 AC: 1538 AN: 2108

Alfa AF: 0.717 Hom.: 40703

Bravo AF: 0.773

Asia WGS AF: 0.797 AC: 2764 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.28
PhyloP100		0.49
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: rs6437002; hg19: chr2-232025284;