rs34628045
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1
The NM_001378454.1(ALMS1):βc.1574_1576delβ(p.Pro525del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,613,222 control chromosomes in the GnomAD database, including 114,241 homozygotes. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.43 ( 15344 hom., cov: 0)
Exomes π: 0.36 ( 98897 hom. )
Consequence
ALMS1
NM_001378454.1 inframe_deletion
NM_001378454.1 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.58
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001378454.1. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 2-73448097-TCTC-T is Benign according to our data. Variant chr2-73448097-TCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 210124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.1574_1576del | p.Pro525del | inframe_deletion | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.1577_1579del | p.Pro526del | inframe_deletion | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.1574_1576del | p.Pro525del | inframe_deletion | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.430 AC: 65206AN: 151534Hom.: 15308 Cov.: 0
GnomAD3 genomes
?
AF:
AC:
65206
AN:
151534
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
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.363 AC: 531038AN: 1461570Hom.: 98897 AF XY: 0.363 AC XY: 263686AN XY: 727106
GnomAD4 exome
AF:
AC:
531038
AN:
1461570
Hom.:
AF XY:
AC XY:
263686
AN XY:
727106
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.431 AC: 65303AN: 151652Hom.: 15344 Cov.: 0 AF XY: 0.425 AC XY: 31473AN XY: 74092
GnomAD4 genome
?
AF:
AC:
65303
AN:
151652
Hom.:
Cov.:
0
AF XY:
AC XY:
31473
AN XY:
74092
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 06, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 22, 2023 | The p.Pro525del variant in ALMS1 is classified as benign because it has been identified in 63.8% (26295/41186) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1. - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 05, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at