1-21687278-G-A

Position:

• chr1-21687278-G-A

Variant summary

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

The NM_032236.8(USP48):​c.3010-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,592,588 control chromosomes in the GnomAD database, including 171,615 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.44 (15316 hom., cov: 32)
  • Exomes 𝑓: 0.46 (156299 hom.)
• Consequence: USP48 NM_032236.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

USP48 (HGNC:18533): (ubiquitin specific peptidase 48) This gene encodes a protein containing domains that associate it with the peptidase family C19, also known as family 2 of ubiquitin carboxyl-terminal hydrolases. Family members function as deubiquitinating enzymes, recognizing and hydrolyzing the peptide bond at the C-terminal glycine of ubiquitin. Enzymes in peptidase family C19 are involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP48	NM_032236.8	c.3010-39C>T		intron_variant		ENST00000308271.14	NP_115612.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP48	ENST00000308271.14	c.3010-39C>T		intron_variant		1	NM_032236.8	ENSP00000309262	P1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66791 AN: 151950 Hom.: 15307 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.457

GnomAD3 exomes AF: 0.499 AC: 114052 AN: 228358 Hom.: 29966 AF XY: 0.489 AC XY: 60253 AN XY: 123278

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.669

Gnomad SAS exome AF: 0.458

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.461 AC: 664045 AN: 1440520 Hom.: 156299 Cov.: 28 AF XY: 0.460 AC XY: 329149 AN XY: 716034

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.719

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.439 AC: 66813 AN: 152068 Hom.: 15316 Cov.: 32 AF XY: 0.444 AC XY: 32973 AN XY: 74334

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.454

Alfa AF: 0.450 Hom.: 27209

Bravo AF: 0.454

Asia WGS AF: 0.522 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.35
BranchPoint Hunter		0.0

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: rs10493008; hg19: chr1-22013771;