rs11853548
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_032808.7(LINGO1):c.1575C>T(p.Pro525=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,613,946 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 33 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 40 hom. )
Consequence
LINGO1
NM_032808.7 synonymous
NM_032808.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.89
Genes affected
LINGO1 (HGNC:21205): (leucine rich repeat and Ig domain containing 1) Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within generation of neurons and protein kinase B signaling. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. Implicated in autosomal recessive non-syndromic intellectual disability and glaucoma. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 15-77614332-G-A is Benign according to our data. Variant chr15-77614332-G-A is described in ClinVar as [Benign]. Clinvar id is 778558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.89 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1812/152346) while in subpopulation AFR AF= 0.0409 (1701/41582). AF 95% confidence interval is 0.0393. There are 33 homozygotes in gnomad4. There are 843 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LINGO1 | NM_032808.7 | c.1575C>T | p.Pro525= | synonymous_variant | 2/2 | ENST00000355300.7 | |
LOC105370906 | XR_001751806.2 | n.689-15953G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LINGO1 | ENST00000355300.7 | c.1575C>T | p.Pro525= | synonymous_variant | 2/2 | 1 | NM_032808.7 | A1 | |
LINGO1 | ENST00000561030.5 | c.1557C>T | p.Pro519= | synonymous_variant | 4/4 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0119 AC: 1805AN: 152228Hom.: 33 Cov.: 33
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GnomAD3 exomes AF: 0.00315 AC: 783AN: 248782Hom.: 16 AF XY: 0.00241 AC XY: 326AN XY: 134994
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GnomAD4 exome AF: 0.00120 AC: 1756AN: 1461600Hom.: 40 Cov.: 31 AF XY: 0.00103 AC XY: 752AN XY: 727078
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GnomAD4 genome ? AF: 0.0119 AC: 1812AN: 152346Hom.: 33 Cov.: 33 AF XY: 0.0113 AC XY: 843AN XY: 74498
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
LINGO1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 06, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
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