1-55212826-G-C

Variant names:

• chr1-55212826-G-C
• rs287235
• NM_015306.3:c.324+1964C>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.324+1964C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,024 control chromosomes in the GnomAD database, including 37,706 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 0.68 (37706 hom., cov: 31)
• Consequence: USP24 NM_015306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP24	NM_015306.3	c.324+1964C>G		intron_variant	Intron 1 of 67	ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.324+1964C>G		intron_variant	Intron 1 of 67	5	NM_015306.3	ENSP00000294383.5
USP24	ENST00000484447.6	c.324+1964C>G		intron_variant	Intron 1 of 67	3		ENSP00000489026.2

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103977 AN: 151906 Hom.: 37697 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.684 AC: 104012 AN: 152024 Hom.: 37706 Cov.: 31 AF XY: 0.692 AC XY: 51444 AN XY: 74314

African (AFR) AF: 0.425 AC: 17605 AN: 41396

American (AMR) AF: 0.822 AC: 12559 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2578 AN: 3470

East Asian (EAS) AF: 0.904 AC: 4677 AN: 5176

South Asian (SAS) AF: 0.863 AC: 4160 AN: 4820

European-Finnish (FIN) AF: 0.777 AC: 8214 AN: 10574

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51726 AN: 68000

Other (OTH) AF: 0.738 AC: 1557 AN: 2110

Alfa AF: 0.612 Hom.: 1957

Bravo AF: 0.675

Asia WGS AF: 0.853 AC: 2967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.43
PhyloP100		0.48
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: rs287235; hg19: chr1-55678499;