rs201109126
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001378454.1(ALMS1):c.11668+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,611,970 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 intron
NM_001378454.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.27
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 Likely_benign. Variant got -3 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 2-73599538-A-G is Benign according to our data. Variant chr2-73599538-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 550830.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.11668+17A>G | intron_variant | ENST00000613296.6 | |||
ALMS1 | NM_015120.4 | c.11668+17A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.11668+17A>G | intron_variant | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248402Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134790
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GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459640Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726224
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GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74492
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Alstrom syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Feb 24, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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