2-73385903-TGGAGGAGGAGGAGGAGGAGGAGGAGGA-TGGAGGA
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP3BP6
The NM_001378454.1(ALMS1):c.54_74delGGAGGAGGAGGAGGAGGAGGA(p.Glu19_Glu25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 701,370 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E18E) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000042 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 disruptive_inframe_deletion
NM_001378454.1 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.45
Publications
7 publications found
Genes affected
ALMS1 (HGNC:428): (ALMS1 centrosome and basal body associated protein) This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]
ALMS1 Gene-Disease associations (from GenCC):
- Alstrom syndromeInheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_001378454.1
BP6
Variant 2-73385903-TGGAGGAGGAGGAGGAGGAGGA-T is Benign according to our data. Variant chr2-73385903-TGGAGGAGGAGGAGGAGGAGGA-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 550448.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001378454.1. 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 |
|---|---|---|---|---|---|---|---|---|---|
| ALMS1 | MANE Select | c.54_74delGGAGGAGGAGGAGGAGGAGGA | p.Glu19_Glu25del | disruptive_inframe_deletion | Exon 1 of 23 | NP_001365383.1 | Q8TCU4-1 | ||
| ALMS1 | c.54_74delGGAGGAGGAGGAGGAGGAGGA | p.Glu19_Glu25del | disruptive_inframe_deletion | Exon 1 of 23 | NP_055935.4 | Q8TCU4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ALMS1 | TSL:1 MANE Select | c.54_74delGGAGGAGGAGGAGGAGGAGGA | p.Glu19_Glu25del | disruptive_inframe_deletion | Exon 1 of 23 | ENSP00000482968.1 | Q8TCU4-1 | ||
| ALMS1 | TSL:1 | c.54_74delGGAGGAGGAGGAGGAGGAGGA | p.Glu19_Glu25del | disruptive_inframe_deletion | Exon 1 of 22 | ENSP00000478155.1 | A0A087WTU9 | ||
| ALMS1 | TSL:5 | c.54_74delGGAGGAGGAGGAGGAGGAGGA | p.Glu19_Glu25del | disruptive_inframe_deletion | Exon 1 of 16 | ENSP00000479094.1 | A0A087WV20 |
Frequencies
GnomAD3 genomes 0.0000418 AC: 6AN: 143530Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
6
AN:
143530
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000430 AC: 24AN: 557736Hom.: 0 AF XY: 0.0000504 AC XY: 15AN XY: 297828 show subpopulations
GnomAD4 exome
AF:
AC:
24
AN:
557736
Hom.:
AF XY:
AC XY:
15
AN XY:
297828
show subpopulations
African (AFR)
AF:
AC:
0
AN:
15796
American (AMR)
AF:
AC:
0
AN:
31236
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
17644
East Asian (EAS)
AF:
AC:
0
AN:
30670
South Asian (SAS)
AF:
AC:
4
AN:
55944
European-Finnish (FIN)
AF:
AC:
2
AN:
36320
Middle Eastern (MID)
AF:
AC:
0
AN:
2422
European-Non Finnish (NFE)
AF:
AC:
16
AN:
337584
Other (OTH)
AF:
AC:
2
AN:
30120
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.548
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
6
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<30
30-35
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Age
GnomAD4 genome 0.0000418 AC: 6AN: 143634Hom.: 0 Cov.: 0 AF XY: 0.0000574 AC XY: 4AN XY: 69662 show subpopulations
GnomAD4 genome
AF:
AC:
6
AN:
143634
Hom.:
Cov.:
0
AF XY:
AC XY:
4
AN XY:
69662
show subpopulations
African (AFR)
AF:
AC:
1
AN:
39968
American (AMR)
AF:
AC:
3
AN:
14700
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3322
East Asian (EAS)
AF:
AC:
1
AN:
4584
South Asian (SAS)
AF:
AC:
0
AN:
4264
European-Finnish (FIN)
AF:
AC:
0
AN:
9398
Middle Eastern (MID)
AF:
AC:
0
AN:
266
European-Non Finnish (NFE)
AF:
AC:
1
AN:
64334
Other (OTH)
AF:
AC:
0
AN:
1972
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
3
1
Alstrom syndrome (4)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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