GeneBe

rs55889738

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001378454.1(ALMS1):​c.48_74delGGAGGAGGAGGAGGAGGAGGAGGAGGA​(p.Glu17_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 0.0000128 in 701,276 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ALMS1
NM_001378454.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

Publications

7 publications found
Variant links:
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 syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_001378454.1

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALMS1NM_001378454.1 linkc.48_74delGGAGGAGGAGGAGGAGGAGGAGGAGGA p.Glu17_Glu25del disruptive_inframe_deletion Exon 1 of 23 ENST00000613296.6 NP_001365383.1
ALMS1NM_015120.4 linkc.48_74delGGAGGAGGAGGAGGAGGAGGAGGAGGA p.Glu17_Glu25del disruptive_inframe_deletion Exon 1 of 23 NP_055935.4 Q8TCU4
LOC105374804XR_007087045.1 linkn.-249_-223delTCCTCCTCCTCCTCCTCCTCCTCCTCC upstream_gene_variant
LOC105374804XR_007087053.1 linkn.-249_-223delTCCTCCTCCTCCTCCTCCTCCTCCTCC upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALMS1ENST00000613296.6 linkc.48_74delGGAGGAGGAGGAGGAGGAGGAGGAGGA p.Glu17_Glu25del disruptive_inframe_deletion Exon 1 of 23 1 NM_001378454.1 ENSP00000482968.1 Q8TCU4-1

Frequencies

GnomAD3 genomes
AF:
0.00000697
AC:
1
AN:
143532
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000155
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000143
AC:
8
AN:
557744
Hom.:
0
AF XY:
0.0000101
AC XY:
3
AN XY:
297830
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
15796
American (AMR)
AF:
0.00
AC:
0
AN:
31236
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
17646
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30670
South Asian (SAS)
AF:
0.00
AC:
0
AN:
55946
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36320
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2422
European-Non Finnish (NFE)
AF:
0.0000237
AC:
8
AN:
337588
Other (OTH)
AF:
0.00
AC:
0
AN:
30120
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
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
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000697
AC:
1
AN:
143532
Hom.:
0
Cov.:
0
AF XY:
0.0000144
AC XY:
1
AN XY:
69544
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
39854
American (AMR)
AF:
0.00
AC:
0
AN:
14682
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3322
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4598
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4270
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9398
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
282
European-Non Finnish (NFE)
AF:
0.0000155
AC:
1
AN:
64346
Other (OTH)
AF:
0.00
AC:
0
AN:
1954
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Apr 19, 2021
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Not observed in large population cohorts (Lek et al., 2016); In-frame deletion of 10 amino acids in a repeat region; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.4
Mutation Taster
=172/28
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs55889738; hg19: chr2-73613031; API