rs1516086

Positions:

• chr2-218566812-G-A
• chr2-218566812-G-C
• chr2-218566812-G-T

Variant summary

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

The NM_020935.3(USP37):​c.-230+1366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,008 control chromosomes in the GnomAD database, including 19,537 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 0.46 (19537 hom., cov: 32)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP37	NM_020935.3	c.-230+1366C>T		intron_variant		ENST00000258399.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP37	ENST00000258399.8	c.-230+1366C>T		intron_variant		1	NM_020935.3	P1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70547 AN: 151884 Hom.: 19537 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.464 AC: 70541 AN: 152008 Hom.: 19537 Cov.: 32 AF XY: 0.472 AC XY: 35045 AN XY: 74294

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.519

Alfa AF: 0.501 Hom.: 7159

Bravo AF: 0.446

Asia WGS AF: 0.689 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.45

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: rs1516086; hg19: chr2-219431535;