rs10498059

Positions:

• chr2-218477182-T-C
• chr2-218477182-T-G

Variant summary

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

The NM_020935.3(USP37):​c.1902-201A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,350 control chromosomes in the GnomAD database, including 119 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 0.034 (119 hom., cov: 33)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

Genes affected

USP37 (HGNC:20063): (ubiquitin specific peptidase 37) Enables cysteine-type endopeptidase activity; protein kinase binding activity; and thiol-dependent deubiquitinase. Involved in G1/S transition of mitotic cell cycle; protein deubiquitination; and regulation of DNA replication. Located in nucleus. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP37	NM_020935.3	c.1902-201A>G		intron_variant		ENST00000258399.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP37	ENST00000258399.8	c.1902-201A>G		intron_variant		1	NM_020935.3	P1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5200 AN: 152232 Hom.: 118 Cov.: 33

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0342 AC: 5205 AN: 152350 Hom.: 119 Cov.: 33 AF XY: 0.0338 AC XY: 2522 AN XY: 74508

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.0270

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0237 Hom.: 20

Bravo AF: 0.0338

Asia WGS AF: 0.0690 AC: 239 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.76
DANN	Benign	0.73

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: rs10498059; hg19: chr2-219341905;