3-66380680-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015541.3(LRIG1):c.2952C>T(p.Ala984=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,614,162 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 44 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 34 hom. )
Consequence
LRIG1
NM_015541.3 synonymous
NM_015541.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.251
Genes affected
LRIG1 (HGNC:17360): (leucine rich repeats and immunoglobulin like domains 1) Predicted to act upstream of or within several processes, including innervation; otolith morphogenesis; and sensory perception of sound. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]
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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=-0.81).
BP6
?
Variant 3-66380680-G-A is Benign according to our data. Variant chr3-66380680-G-A is described in ClinVar as [Benign]. Clinvar id is 791935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.251 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1704/152302) while in subpopulation AFR AF= 0.0385 (1600/41552). AF 95% confidence interval is 0.0369. There are 44 homozygotes in gnomad4. There are 787 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1697 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRIG1 | NM_015541.3 | c.2952C>T | p.Ala984= | synonymous_variant | 18/19 | ENST00000273261.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRIG1 | ENST00000273261.8 | c.2952C>T | p.Ala984= | synonymous_variant | 18/19 | 1 | NM_015541.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0112 AC: 1697AN: 152184Hom.: 45 Cov.: 33
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GnomAD3 exomes AF: 0.00296 AC: 743AN: 251322Hom.: 11 AF XY: 0.00213 AC XY: 289AN XY: 135870
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GnomAD4 exome AF: 0.00130 AC: 1902AN: 1461860Hom.: 34 Cov.: 33 AF XY: 0.00120 AC XY: 874AN XY: 727226
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
LRIG1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 23, 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 | May 15, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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