NM_001378454.1:c.60G>A
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001378454.1(ALMS1):c.60G>A(p.Glu20Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000557 in 898,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 synonymous
NM_001378454.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.443
Publications
1 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 Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 2-73385928-G-A is Benign according to our data. Variant chr2-73385928-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 412662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.443 with no splicing effect.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ALMS1 | NM_001378454.1 | MANE Select | c.60G>A | p.Glu20Glu | synonymous | Exon 1 of 23 | NP_001365383.1 | ||
| ALMS1 | NM_015120.4 | c.60G>A | p.Glu20Glu | synonymous | Exon 1 of 23 | NP_055935.4 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ALMS1 | ENST00000613296.6 | TSL:1 MANE Select | c.60G>A | p.Glu20Glu | synonymous | Exon 1 of 23 | ENSP00000482968.1 | ||
| ALMS1 | ENST00000484298.5 | TSL:1 | c.60G>A | p.Glu20Glu | synonymous | Exon 1 of 22 | ENSP00000478155.1 | ||
| ALMS1 | ENST00000614410.4 | TSL:5 | c.60G>A | p.Glu20Glu | synonymous | Exon 1 of 16 | ENSP00000479094.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000513 AC: 7AN: 136516 AF XY: 0.0000552 show subpopulations
GnomAD2 exomes
AF:
AC:
7
AN:
136516
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000557 AC: 5AN: 898338Hom.: 0 Cov.: 12 AF XY: 0.00000650 AC XY: 3AN XY: 461650 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
5
AN:
898338
Hom.:
Cov.:
12
AF XY:
AC XY:
3
AN XY:
461650
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
21134
American (AMR)
AF:
AC:
1
AN:
34534
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
21462
East Asian (EAS)
AF:
AC:
0
AN:
33346
South Asian (SAS)
AF:
AC:
0
AN:
67402
European-Finnish (FIN)
AF:
AC:
0
AN:
46284
Middle Eastern (MID)
AF:
AC:
0
AN:
3800
European-Non Finnish (NFE)
AF:
AC:
4
AN:
628808
Other (OTH)
AF:
AC:
0
AN:
41568
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0184789), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.345
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
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65-70
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
3
not provided (3)
-
-
1
Alstrom syndrome (1)
-
-
1
Cardiovascular phenotype (1)
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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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