15-72474873-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGC
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_005744.5(ARIH1):c.255_257delCGG(p.Gly86del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,406,666 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G85G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00069 ( 0 hom. )
Consequence
ARIH1
NM_005744.5 disruptive_inframe_deletion
NM_005744.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.74
Publications
1 publications found
Genes affected
ARIH1 (HGNC:689): (ariadne RBR E3 ubiquitin protein ligase 1) Enables enzyme binding activity; ubiquitin-protein transferase activity; and zinc ion binding activity. Involved in protein ubiquitination. Located in Lewy body; cytoplasm; and nuclear body. Colocalizes with cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005744.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ARIH1 | NM_005744.5 | MANE Select | c.255_257delCGG | p.Gly86del | disruptive_inframe_deletion | Exon 1 of 14 | NP_005735.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ARIH1 | ENST00000379887.9 | TSL:1 MANE Select | c.255_257delCGG | p.Gly86del | disruptive_inframe_deletion | Exon 1 of 14 | ENSP00000369217.4 | ||
| ARIH1 | ENST00000915026.1 | c.255_257delCGG | p.Gly86del | disruptive_inframe_deletion | Exon 1 of 14 | ENSP00000585085.1 | |||
| ARIH1 | ENST00000915024.1 | c.255_257delCGG | p.Gly86del | disruptive_inframe_deletion | Exon 1 of 14 | ENSP00000585083.1 |
Frequencies
GnomAD3 genomes 0.00000668 AC: 1AN: 149690Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
149690
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00285 AC: 176AN: 61656 AF XY: 0.00293 show subpopulations
GnomAD2 exomes
AF:
AC:
176
AN:
61656
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000691 AC: 868AN: 1256872Hom.: 0 AF XY: 0.000846 AC XY: 521AN XY: 615750 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
868
AN:
1256872
Hom.:
AF XY:
AC XY:
521
AN XY:
615750
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
7
AN:
26106
American (AMR)
AF:
AC:
44
AN:
21226
Ashkenazi Jewish (ASJ)
AF:
AC:
30
AN:
20072
East Asian (EAS)
AF:
AC:
6
AN:
27714
South Asian (SAS)
AF:
AC:
250
AN:
56826
European-Finnish (FIN)
AF:
AC:
63
AN:
42330
Middle Eastern (MID)
AF:
AC:
2
AN:
4950
European-Non Finnish (NFE)
AF:
AC:
431
AN:
1006428
Other (OTH)
AF:
AC:
35
AN:
51220
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.251
Heterozygous variant carriers
0
128
255
383
510
638
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000668 AC: 1AN: 149794Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73142 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
149794
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
73142
show subpopulations
African (AFR)
AF:
AC:
0
AN:
40762
American (AMR)
AF:
AC:
0
AN:
15092
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3442
East Asian (EAS)
AF:
AC:
0
AN:
5076
South Asian (SAS)
AF:
AC:
0
AN:
4666
European-Finnish (FIN)
AF:
AC:
0
AN:
10172
Middle Eastern (MID)
AF:
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67334
Other (OTH)
AF:
AC:
0
AN:
2070
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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