rs2278226
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002317.7(LOX):āc.225C>Gā(p.Ala75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,552,762 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. A75A) has been classified as Likely benign.
Frequency
Consequence
NM_002317.7 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOX | NM_002317.7 | c.225C>G | p.Ala75= | synonymous_variant | 1/7 | ENST00000231004.5 | |
SRFBP1 | XM_017009111.3 | c.*2436G>C | 3_prime_UTR_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOX | ENST00000231004.5 | c.225C>G | p.Ala75= | synonymous_variant | 1/7 | 1 | NM_002317.7 | P1 | |
LOX | ENST00000639739.2 | c.225C>G | p.Ala75= | synonymous_variant, NMD_transcript_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00382 AC: 581AN: 152102Hom.: 13 Cov.: 32
GnomAD3 exomes AF: 0.0117 AC: 1712AN: 146686Hom.: 53 AF XY: 0.00995 AC XY: 804AN XY: 80802
GnomAD4 exome AF: 0.00294 AC: 4111AN: 1400552Hom.: 126 Cov.: 33 AF XY: 0.00280 AC XY: 1942AN XY: 692438
GnomAD4 genome ? AF: 0.00380 AC: 579AN: 152210Hom.: 13 Cov.: 32 AF XY: 0.00472 AC XY: 351AN XY: 74410
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 17, 2017 | Variant summary: The LOX c.225C>G (p.Ala75Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 234/21640 control chromosomes (7 homozygotes) from ExAC at a frequency of 0.0108133, which is approximately 649 times the estimated maximal expected allele frequency of a pathogenic LOX variant (0.0000167), strongly indicating this variant is likely a benign polymorphism. Taken together, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Aortic aneurysm, familial thoracic 10 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 08, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Feb 08, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 13, 2019 | 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