chr2-73385848-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001378454.1(ALMS1):c.-21C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000881 in 715,324 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 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 5_prime_UTR
NM_001378454.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.897
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 -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 2-73385848-C-T is Benign according to our data. Variant chr2-73385848-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 509001.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.-21C>T | 5_prime_UTR_variant | 1/23 | ENST00000613296.6 | ||
ALMS1 | NM_015120.4 | c.-21C>T | 5_prime_UTR_variant | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.-21C>T | 5_prime_UTR_variant | 1/23 | 1 | NM_001378454.1 | P3 | ||
ALMS1 | ENST00000484298.5 | c.-21C>T | 5_prime_UTR_variant | 1/22 | 1 | A2 | |||
ALMS1 | ENST00000614410.4 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 151994Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000725 AC: 9AN: 124146Hom.: 0 AF XY: 0.0000445 AC XY: 3AN XY: 67364
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GnomAD4 exome AF: 0.0000497 AC: 28AN: 563222Hom.: 0 Cov.: 6 AF XY: 0.0000461 AC XY: 14AN XY: 303674
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GnomAD4 genome AF: 0.000230 AC: 35AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at