1-55164531-A-G

Position:

• chr1-55164531-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015306.3(USP24):​c.927+1354T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,870 control chromosomes in the GnomAD database, including 43,043 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 0.74 (43043 hom., cov: 31)
• Consequence: USP24 NM_015306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP24	NM_015306.3	c.927+1354T>C		intron_variant		ENST00000294383.7	NP_056121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7	c.927+1354T>C		intron_variant		5	NM_015306.3	ENSP00000294383	P1
USP24	ENST00000484447.6	c.927+1354T>C		intron_variant		3		ENSP00000489026

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112595 AN: 151752 Hom.: 43024 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.742 AC: 112653 AN: 151870 Hom.: 43043 Cov.: 31 AF XY: 0.749 AC XY: 55585 AN XY: 74230

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.780

Alfa AF: 0.794 Hom.: 97394

Bravo AF: 0.735

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.5
DANN	Benign	0.83

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: rs1024305; hg19: chr1-55630204; COSMIC: COSV53764763;