rs594226

Positions:

• chr1-55107194-G-A
• chr1-55107194-G-C
• chr1-55107194-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.4762+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,572,172 control chromosomes in the GnomAD database, including 450,858 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 0.65 (35912 hom., cov: 31)
  • Exomes 𝑓: 0.76 (414946 hom.)
• Consequence: USP24 NM_015306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP24	NM_015306.3	c.4762+45C>T		intron_variant		ENST00000294383.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP24	ENST00000294383.7	c.4762+45C>T		intron_variant		5	NM_015306.3	P1
USP24	ENST00000484447.6	c.4762+45C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99581 AN: 151962 Hom.: 35903 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.720

GnomAD3 exomes AF: 0.768 AC: 164106 AN: 213754 Hom.: 64940 AF XY: 0.772 AC XY: 88472 AN XY: 114528

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.880

Gnomad ASJ exome AF: 0.729

Gnomad EAS exome AF: 0.909

Gnomad SAS exome AF: 0.829

Gnomad FIN exome AF: 0.771

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.760 AC: 1079506 AN: 1420092 Hom.: 414946 Cov.: 28 AF XY: 0.763 AC XY: 536621 AN XY: 703184

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.727

Gnomad4 EAS exome AF: 0.902

Gnomad4 SAS exome AF: 0.829

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.655 AC: 99605 AN: 152080 Hom.: 35912 Cov.: 31 AF XY: 0.664 AC XY: 49333 AN XY: 74346

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.723

Alfa AF: 0.672 Hom.: 7064

Bravo AF: 0.644

Asia WGS AF: 0.842 AC: 2926 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	1.4
DANN	Benign	0.43

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: rs594226; hg19: chr1-55572867; COSMIC: COSV53764561;