rs754948598
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The ENST00000371817.8(COL5A1):c.1402G>A(p.Glu468Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,930 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E468Q) has been classified as Likely benign.
Frequency
Consequence
ENST00000371817.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.1402G>A | p.Glu468Lys | missense_variant | 10/66 | ENST00000371817.8 | NP_000084.3 | |
COL5A1 | NM_001278074.1 | c.1402G>A | p.Glu468Lys | missense_variant | 10/66 | NP_001265003.1 | ||
COL5A1 | XM_017014266.3 | c.1402G>A | p.Glu468Lys | missense_variant | 10/65 | XP_016869755.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.1402G>A | p.Glu468Lys | missense_variant | 10/66 | 1 | NM_000093.5 | ENSP00000360882 | P4 | |
COL5A1 | ENST00000371820.4 | c.1402G>A | p.Glu468Lys | missense_variant | 10/66 | 2 | ENSP00000360885 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251284Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135864
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461714Hom.: 1 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727174
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2022 | Identified as homozygous in a patient with ischemia due to spontaneous, recurrent, bilateral carotid artery dissections; this patient was also heterozygous for a second variant in COL5A1 (Qin et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; HGMD); This variant is associated with the following publications: (PMID: 22696272, 28093518) - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 02, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at