chr2-231160570-G-A

Position:

• chr2-231160570-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD1	NM_002807.4	c.2219-770G>A		intron_variant		ENST00000308696.11
PSMD1	NM_001191037.2	c.2219-770G>A		intron_variant
PSMD1	NR_034059.2	n.2208-770G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD1	ENST00000308696.11	c.2219-770G>A		intron_variant		1	NM_002807.4	P1

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

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.730

Alfa AF: 0.704 Hom.: 20625

Bravo AF: 0.773

Asia WGS AF: 0.797 AC: 2764 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.28

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: rs6437002; hg19: chr2-232025284;