rs6714092

Positions:

• chr2-218540882-C-T

Variant summary

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

The NM_020935.3(USP37):​c.680+5339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,140 control chromosomes in the GnomAD database, including 365 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 0.057 (365 hom., cov: 32)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP37	NM_020935.3	c.680+5339G>A		intron_variant		ENST00000258399.8	NP_065986.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP37	ENST00000258399.8	c.680+5339G>A		intron_variant		1	NM_020935.3	ENSP00000258399	P1

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8615 AN: 152026 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0444

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0567 AC: 8628 AN: 152140 Hom.: 365 Cov.: 32 AF XY: 0.0553 AC XY: 4115 AN XY: 74378

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0521 Hom.: 48

Bravo AF: 0.0599

Asia WGS AF: 0.0730 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.71

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: rs6714092; hg19: chr2-219405605;