1-55081222-T-C

Variant names:

• chr1-55081222-T-C
• rs683880
• NM_015306.3:c.7078+100A>G

Variant summary

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

The NM_015306.3(USP24):​c.7078+100A>G 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 1,204,442 control chromosomes in the GnomAD database, including 346,276 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 (35876 hom., cov: 33)
  • Exomes 𝑓: 0.76 (310400 hom.)
• Consequence: USP24 NM_015306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015306.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP24	NM_015306.3	MANE Select	c.7078+100A>G		intron	N/A	NP_056121.2	Q9UPU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP24	ENST00000294383.7	TSL:5 MANE Select	c.7078+100A>G		intron	N/A	ENSP00000294383.5	Q9UPU5
	USP24	ENST00000927917.1		c.7075+100A>G		intron	N/A	ENSP00000597976.1
	USP24	ENST00000484447.6	TSL:3	c.7078+100A>G		intron	N/A	ENSP00000489026.2	A0A0U1RQI9

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99478 AN: 151988 Hom.: 35867 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.717

GnomAD4 exome AF: 0.763 AC: 803267 AN: 1052334 Hom.: 310400 AF XY: 0.766 AC XY: 405266 AN XY: 528902

African (AFR) AF: 0.308 AC: 7362 AN: 23886

American (AMR) AF: 0.865 AC: 26151 AN: 30248

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 14324 AN: 19712

East Asian (EAS) AF: 0.901 AC: 32418 AN: 35982

South Asian (SAS) AF: 0.828 AC: 50780 AN: 61326

European-Finnish (FIN) AF: 0.774 AC: 35312 AN: 45618

Middle Eastern (MID) AF: 0.835 AC: 3928 AN: 4702

European-Non Finnish (NFE) AF: 0.763 AC: 598685 AN: 785158

Other (OTH) AF: 0.751 AC: 34307 AN: 45702

GnomAD4 genome AF: 0.654 AC: 99501 AN: 152108 Hom.: 35876 Cov.: 33 AF XY: 0.663 AC XY: 49288 AN XY: 74350

African (AFR) AF: 0.324 AC: 13427 AN: 41476

American (AMR) AF: 0.813 AC: 12434 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2526 AN: 3470

East Asian (EAS) AF: 0.907 AC: 4702 AN: 5182

South Asian (SAS) AF: 0.843 AC: 4066 AN: 4824

European-Finnish (FIN) AF: 0.770 AC: 8144 AN: 10574

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51738 AN: 67970

Other (OTH) AF: 0.721 AC: 1525 AN: 2116

Alfa AF: 0.720 Hom.: 17587

Bravo AF: 0.643

Asia WGS AF: 0.840 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.40
PhyloP100		-0.40
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs683880;

hg19: chr1-55546895;

COSMIC: COSV53764149;

COSMIC: COSV53764149;