rs2244291

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022832.4(USP46):​c.723-259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 152,166 control chromosomes in the GnomAD database, including 856 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 0.093 ( 856 hom., cov: 32)

Consequence

USP46
NM_022832.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.328
Variant links:
Genes affected
USP46 (HGNC:20075): (ubiquitin specific peptidase 46) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
USP46NM_022832.4 linkuse as main transcriptc.723-259A>G intron_variant ENST00000441222.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
USP46ENST00000441222.8 linkuse as main transcriptc.723-259A>G intron_variant 1 NM_022832.4 P1P62068-1

Frequencies

GnomAD3 genomes
AF:
0.0928
AC:
14108
AN:
152048
Hom.:
854
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0193
Gnomad AMI
AF:
0.102
Gnomad AMR
AF:
0.124
Gnomad ASJ
AF:
0.0888
Gnomad EAS
AF:
0.214
Gnomad SAS
AF:
0.159
Gnomad FIN
AF:
0.160
Gnomad MID
AF:
0.0759
Gnomad NFE
AF:
0.107
Gnomad OTH
AF:
0.0828
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0927
AC:
14104
AN:
152166
Hom.:
856
Cov.:
32
AF XY:
0.0965
AC XY:
7175
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0192
Gnomad4 AMR
AF:
0.124
Gnomad4 ASJ
AF:
0.0888
Gnomad4 EAS
AF:
0.215
Gnomad4 SAS
AF:
0.159
Gnomad4 FIN
AF:
0.160
Gnomad4 NFE
AF:
0.107
Gnomad4 OTH
AF:
0.0852
Alfa
AF:
0.100
Hom.:
1033
Bravo
AF:
0.0858
Asia WGS
AF:
0.193
AC:
671
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.6
DANN
Benign
0.57

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

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

Other links and lift over

dbSNP: rs2244291; hg19: chr4-53468479; API