rs201474138
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001378454.1(ALMS1):c.3945G>A(p.Ala1315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000524 in 1,604,130 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: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 synonymous
NM_001378454.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.155
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 2-73450472-G-A is Benign according to our data. Variant chr2-73450472-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 529404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.155 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000424 (62/1461634) while in subpopulation AFR AF= 0.00102 (34/33470). AF 95% confidence interval is 0.000746. There are 0 homozygotes in gnomad4_exome. There are 27 alleles in male gnomad4_exome subpopulation. Median coverage is 39. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.3945G>A | p.Ala1315= | synonymous_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.3948G>A | p.Ala1316= | synonymous_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.3945G>A | p.Ala1315= | synonymous_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000155 AC: 22AN: 142380Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000763 AC: 19AN: 249112Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135140
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461634Hom.: 0 Cov.: 39 AF XY: 0.0000371 AC XY: 27AN XY: 727130
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GnomAD4 genome ? AF: 0.000154 AC: 22AN: 142496Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 14AN XY: 69638
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Alstrom syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 30, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 06, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 14, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at