rs838552

Positions:

• chr2-233513383-A-G

Variant summary

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

The NM_001365479.2(USP40):​c.2384-761T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,074 control chromosomes in the GnomAD database, including 5,545 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 0.26 (5545 hom., cov: 32)
• Consequence: USP40 NM_001365479.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

Genes affected

USP40 (HGNC:20069): (ubiquitin specific peptidase 40) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP40 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP40	NM_001365479.2	c.2384-761T>C		intron_variant		ENST00000678225.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP40	ENST00000678225.2	c.2384-761T>C		intron_variant			NM_001365479.2	P3
USP40	ENST00000427112.6	c.2381-761T>C		intron_variant		1		A1
USP40	ENST00000251722.10	c.2381-761T>C		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38997 AN: 151956 Hom.: 5541 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.257 AC: 39022 AN: 152074 Hom.: 5545 Cov.: 32 AF XY: 0.255 AC XY: 18937 AN XY: 74334

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.229

Alfa AF: 0.219 Hom.: 3544

Bravo AF: 0.254

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
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: rs838552; hg19: chr2-234422029;