rs200491758
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_001378454.1(ALMS1):āc.4134T>Cā(p.Ser1378=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,611,392 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: š 0.00061 ( 0 hom., cov: 32)
Exomes š: 0.000061 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 synonymous
NM_001378454.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00200
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 -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 2-73450661-T-C is Benign according to our data. Variant chr2-73450661-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 392604.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.002 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000608 (91/149578) while in subpopulation AFR AF= 0.00215 (87/40500). AF 95% confidence interval is 0.00178. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.4134T>C | p.Ser1378= | synonymous_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.4137T>C | p.Ser1379= | synonymous_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.4134T>C | p.Ser1378= | synonymous_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000609 AC: 91AN: 149462Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000160 AC: 40AN: 249276Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135218
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461814Hom.: 0 Cov.: 39 AF XY: 0.0000495 AC XY: 36AN XY: 727214
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GnomAD4 genome ? AF: 0.000608 AC: 91AN: 149578Hom.: 0 Cov.: 32 AF XY: 0.000507 AC XY: 37AN XY: 73008
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 05, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 15, 2017 | - - |
Alstrom syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 01, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 11, 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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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