rs594226

Variant names:

• chr1-55107194-G-A
• rs594226
• NM_015306.3:c.4762+45C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-55107194-G-A
• chr1-55107194-G-C
• chr1-55107194-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USP24	NM_015306.3	c.4762+45C>T		intron_variant	Intron 40 of 67	ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.4762+45C>T		intron_variant	Intron 40 of 67	5	NM_015306.3	ENSP00000294383.5
USP24	ENST00000484447.6	c.4762+45C>T		intron_variant	Intron 40 of 67	3		ENSP00000489026.2

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

GnomAD2 exomes AF: 0.768 AC: 164106 AN: 213754 AF XY: 0.772

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 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

African (AFR) AF: 0.310 AC: 9973 AN: 32212

American (AMR) AF: 0.870 AC: 34469 AN: 39640

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 16680 AN: 22936

East Asian (EAS) AF: 0.902 AC: 35442 AN: 39304

South Asian (SAS) AF: 0.829 AC: 64347 AN: 77634

European-Finnish (FIN) AF: 0.774 AC: 40095 AN: 51782

Middle Eastern (MID) AF: 0.828 AC: 4586 AN: 5538

European-Non Finnish (NFE) AF: 0.760 AC: 830036 AN: 1092390

Other (OTH) AF: 0.748 AC: 43878 AN: 58656

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

African (AFR) AF: 0.326 AC: 13523 AN: 41442

American (AMR) AF: 0.814 AC: 12448 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2528 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4695 AN: 5176

South Asian (SAS) AF: 0.844 AC: 4073 AN: 4828

European-Finnish (FIN) AF: 0.771 AC: 8145 AN: 10568

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.761 AC: 51728 AN: 67980

Other (OTH) AF: 0.723 AC: 1528 AN: 2112

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
PhyloP100		-0.052
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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