chr2-73385903-T-TGGAGGAGGAGGA
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2
The NM_001378454.1(ALMS1):c.63_74dupGGAGGAGGAGGA(p.Glu22_Glu25dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001378454.1 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.63_74dupGGAGGAGGAGGA | p.Glu22_Glu25dup | disruptive_inframe_insertion | Exon 1 of 23 | ENST00000613296.6 | NP_001365383.1 | |
ALMS1 | NM_015120.4 | c.63_74dupGGAGGAGGAGGA | p.Glu22_Glu25dup | disruptive_inframe_insertion | Exon 1 of 23 | NP_055935.4 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00128 AC: 183AN: 143526Hom.: 1 Cov.: 0
GnomAD4 exome AF: 0.00250 AC: 1392AN: 557702Hom.: 2 Cov.: 0 AF XY: 0.00239 AC XY: 711AN XY: 297806
GnomAD4 genome AF: 0.00126 AC: 181AN: 143630Hom.: 1 Cov.: 0 AF XY: 0.00145 AC XY: 101AN XY: 69660
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:1
- -
not specified Benign:1
Variant summary: The ALMS1 variant, c.66_74dupGGAGGAGGA (p.Glu26_Glu28dup, also known as c.69_77dup) is located in a Glu repetitive region. The variant allele was found at a frequency of 0.0043 in 83366 control chromosomes, predominantly at a frequency of 0.011 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 5-folds over the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Cardiomyopathy phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.66_74dupGGAGGAGGA in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
Cardiovascular phenotype Benign:1
This alteration is classified as 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at