rs3098198

Positions:

• chr15-50528007-G-A
• chr15-50528007-G-T

Variant summary

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

The NM_203494.5(USP50):​c.936+1790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 150,800 control chromosomes in the GnomAD database, including 23,410 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 0.56 (23410 hom., cov: 28)
• Consequence: USP50 NM_203494.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

Genes affected

USP50 (HGNC:20079): (ubiquitin specific peptidase 50) Enables ubiquitin-like protein-specific protease activity. Acts upstream of or within several processes, including nuclear speck organization; positive regulation of NLRP3 inflammasome complex assembly; and positive regulation of macromolecule metabolic process. Predicted to be active in several cellular components, including dendritic spine; midbody; and postsynaptic density. Predicted to be extrinsic component of endosome membrane and extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP50	NM_203494.5	c.936+1790C>T		intron_variant		ENST00000532404.6	NP_987090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP50	ENST00000532404.6	c.936+1790C>T		intron_variant		5	NM_203494.5	ENSP00000434676.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 83849 AN: 150688 Hom.: 23412 Cov.: 28

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.556 AC: 83888 AN: 150800 Hom.: 23410 Cov.: 28 AF XY: 0.557 AC XY: 40986 AN XY: 73578

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.591

Alfa AF: 0.567 Hom.: 31190

Bravo AF: 0.563

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.3
DANN	Benign	0.52

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: rs3098198; hg19: chr15-50820204;