rs1549339

Variant names:

• chr2-231118112-G-A
• rs1549339
• NM_002807.4:c.1884-20624G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-231118112-G-A
• chr2-231118112-G-T

Variant summary

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

The NM_002807.4(PSMD1):​c.1884-20624G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 149,610 control chromosomes in the GnomAD database, including 15,833 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 (15833 hom., cov: 32)
• Consequence: PSMD1 NM_002807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 13 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]

HTR2B (HGNC:5294): (5-hydroxytryptamine receptor 2B) This gene encodes one of the several different receptors for 5-hydroxytryptamine (serotonin) that belongs to the G-protein coupled receptor 1 family. Serotonin is a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. Serotonin receptors mediate many of the central and peripheral physiologic functions of serotonin, including regulation of cardiovascular functions and impulsive behavior. Population and family-based analyses of a minor allele (glutamine-to-stop substitution, designated Q20*) which blocks expression of this protein, and knockout studies in mice, suggest a role for this gene in impulsivity. However, other factors, such as elevated testosterone levels, may also be involved. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD1	NM_002807.4	c.1884-20624G>A		intron_variant	Intron 16 of 24	ENST00000308696.11	NP_002798.2
HTR2B	NM_000867.5	c.353-4183C>T		intron_variant	Intron 2 of 3	ENST00000258400.4	NP_000858.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD1	ENST00000308696.11	c.1884-20624G>A		intron_variant	Intron 16 of 24	1	NM_002807.4	ENSP00000309474.6
HTR2B	ENST00000258400.4	c.353-4183C>T		intron_variant	Intron 2 of 3	1	NM_000867.5	ENSP00000258400.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 65868 AN: 149506 Hom.: 15816 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.441 AC: 65927 AN: 149610 Hom.: 15833 Cov.: 32 AF XY: 0.445 AC XY: 32591 AN XY: 73176

African (AFR) AF: 0.650 AC: 25526 AN: 39246

American (AMR) AF: 0.357 AC: 5408 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1417 AN: 3468

East Asian (EAS) AF: 0.608 AC: 3146 AN: 5176

South Asian (SAS) AF: 0.443 AC: 2135 AN: 4816

European-Finnish (FIN) AF: 0.458 AC: 4831 AN: 10558

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22141 AN: 67894

Other (OTH) AF: 0.426 AC: 892 AN: 2094

Alfa AF: 0.362 Hom.: 29543

Bravo AF: 0.433

Asia WGS AF: 0.562 AC: 1950 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		-0.022
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: rs1549339; hg19: chr2-231982826;