rs567734

Positions:

• chr1-55108691-G-A
• chr1-55108691-G-C

Variant summary

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

The NM_015306.3(USP24):​c.4571-1261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,104 control chromosomes in the GnomAD database, including 43,099 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 0.74 (43099 hom., cov: 32)
• Consequence: USP24 NM_015306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

Genes affected

USP24 (HGNC:12623): (ubiquitin specific peptidase 24) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP24	NM_015306.3	c.4571-1261C>T		intron_variant		ENST00000294383.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP24	ENST00000294383.7	c.4571-1261C>T		intron_variant		5	NM_015306.3	P1
USP24	ENST00000484447.6	c.4571-1261C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112749 AN: 151986 Hom.: 43081 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.742 AC: 112806 AN: 152104 Hom.: 43099 Cov.: 32 AF XY: 0.749 AC XY: 55690 AN XY: 74370

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.780

Alfa AF: 0.747 Hom.: 5854

Bravo AF: 0.735

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs567734; hg19: chr1-55574364; COSMIC: COSV53764570;