rs625219

Positions:

• chr1-55120008-G-A
• chr1-55120008-G-C
• chr1-55120008-G-T

Variant summary

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

The NM_015306.3(USP24):​c.4508+588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,168 control chromosomes in the GnomAD database, including 57,396 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 0.87 (57396 hom., cov: 30)
• Consequence: USP24 NM_015306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP24	NM_015306.3	c.4508+588C>T		intron_variant		ENST00000294383.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP24	ENST00000294383.7	c.4508+588C>T		intron_variant		5	NM_015306.3	P1
USP24	ENST00000484447.6	c.4508+588C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131983 AN: 152050 Hom.: 57353 Cov.: 30

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.868 AC: 132083 AN: 152168 Hom.: 57396 Cov.: 30 AF XY: 0.871 AC XY: 64815 AN XY: 74388

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.880

Alfa AF: 0.861 Hom.: 8000

Bravo AF: 0.869

Asia WGS AF: 0.952 AC: 3310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.64
DANN	Benign	0.19

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: rs625219; hg19: chr1-55585681; COSMIC: COSV53764610;