chr1-55142332-C-T

Variant names:

• chr1-55142332-C-T
• rs1165226
• NM_015306.3:c.2634+410G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015306.3(USP24):​c.2634+410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,816 control chromosomes in the GnomAD database, including 22,928 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 0.52 (22928 hom., cov: 31)
• Consequence: USP24 NM_015306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP24	NM_015306.3	c.2634+410G>A		intron_variant	Intron 23 of 67	ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.2634+410G>A		intron_variant	Intron 23 of 67	5	NM_015306.3	ENSP00000294383.5
USP24	ENST00000484447.6	c.2634+410G>A		intron_variant	Intron 23 of 67	3		ENSP00000489026.2

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78495 AN: 151698 Hom.: 22930 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.517 AC: 78504 AN: 151816 Hom.: 22928 Cov.: 31 AF XY: 0.519 AC XY: 38533 AN XY: 74192

African (AFR) AF: 0.230 AC: 9501 AN: 41350

American (AMR) AF: 0.671 AC: 10237 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3468

East Asian (EAS) AF: 0.779 AC: 4030 AN: 5176

South Asian (SAS) AF: 0.627 AC: 3010 AN: 4804

European-Finnish (FIN) AF: 0.512 AC: 5379 AN: 10506

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.625 AC: 42426 AN: 67934

Other (OTH) AF: 0.576 AC: 1215 AN: 2110

Alfa AF: 0.594 Hom.: 114396

Bravo AF: 0.515

Asia WGS AF: 0.648 AC: 2253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.22
PhyloP100		-0.55
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: rs1165226; hg19: chr1-55608005; COSMIC: COSV53764692;