rs10189064

chr2-218462777-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020935.3(USP37):c.2527+529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 152,128 control chromosomes in the GnomAD database, including 52 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 0.021 (52 hom., cov: 32)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0207 (3154/152128) while in subpopulation NFE AF= 0.031 (2111/68006). AF 95% confidence interval is 0.0299. There are 52 homozygotes in gnomad4. There are 1379 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3155 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP37	NM_020935.3	c.2527+529C>T		intron_variant		ENST00000258399.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP37	ENST00000258399.8	c.2527+529C>T		intron_variant		1	NM_020935.3	P1
USP37	ENST00000415516.5	c.2245+529C>T		intron_variant		1
USP37	ENST00000418019.5	c.2527+529C>T		intron_variant		1		P1
USP37	ENST00000454775.5	c.2527+529C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3155 AN: 152010 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.00813

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0207 AC: 3154 AN: 152128 Hom.: 52 Cov.: 32 AF XY: 0.0185 AC XY: 1379 AN XY: 74372

Gnomad4 AFR AF: 0.00569

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00813

Gnomad4 NFE AF: 0.0310

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0265 Hom.: 27

Bravo AF: 0.0219

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.9
Dann	Benign	0.68

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: rs10189064; hg19: chr2-219327500;