Variant 1-21704398-C-CA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_032236.8(USP48):c.2385-7_2385-6insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,144,608 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.020 ( 3 hom. )

Consequence

USP48
NM_032236.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.12

Variant links:

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]

USP48 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 1-21704398-C-CA is Benign according to our data. Variant chr1-21704398-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 3354857.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0203 (20304/1002636) while in subpopulation SAS AF= 0.0412 (2181/52996). AF 95% confidence interval is 0.0397. There are 3 homozygotes in gnomad4_exome. There are 10547 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 314 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP48	NM_032236.8 linkuse as main transcript	c.2385-7_2385-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000308271.14	NP_115612.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP48	ENST00000308271.14 linkuse as main transcript	c.2385-7_2385-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032236.8	ENSP00000309262	P1	Q86UV5-1

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

313

AN:

141896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000598

Gnomad EAS

AF:

0.00141

Gnomad SAS

AF:

0.00178

Gnomad FIN

AF:

0.00131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00204

GnomAD3 exomes

AF:

0.0390

AC:

4573

AN:

117276

Hom.:

AF XY:

0.0384

AC XY:

2443

AN XY:

63662

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.0646

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.0496

Gnomad SAS exome

AF:

0.0474

Gnomad FIN exome

AF:

0.0314

Gnomad NFE exome

AF:

0.0306

Gnomad OTH exome

AF:

0.0551

GnomAD4 exome

AF:

0.0203

AC:

20304

AN:

1002636

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

10547

AN XY:

495724

show subpopulations

Gnomad4 AFR exome

AF:

0.0294

Gnomad4 AMR exome

AF:

0.0396

Gnomad4 ASJ exome

AF:

0.0334

Gnomad4 EAS exome

AF:

0.0300

Gnomad4 SAS exome

AF:

0.0412

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0241

GnomAD4 genome

AF:

0.00221

AC:

314

AN:

141972

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

157

AN XY:

68792

show subpopulations

Gnomad4 AFR

AF:

0.00416

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.000598

Gnomad4 EAS

AF:

0.00141

Gnomad4 SAS

AF:

0.00178

Gnomad4 FIN

AF:

0.00131

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

USP48-related condition

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 29, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over