X-108440099-T-TGAAGGAGCTGCGGGAGCC
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_033380.3(COL4A5):c.-25_-8dupAAGGAGCTGCGGGAGCCG variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000124 in 1,171,627 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_033380.3 5_prime_UTR
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.-25_-8dupAAGGAGCTGCGGGAGCCG | 5_prime_UTR_variant | Exon 1 of 53 | ENST00000328300.11 | NP_203699.1 | ||
COL4A5 | NM_000495.5 | c.-25_-8dupAAGGAGCTGCGGGAGCCG | 5_prime_UTR_variant | Exon 1 of 51 | NP_000486.1 | |||
COL4A5 | XM_047441810.1 | c.-401_-384dupAAGGAGCTGCGGGAGCCG | 5_prime_UTR_variant | Exon 1 of 54 | XP_047297766.1 | |||
COL4A5 | XM_047441811.1 | c.-25_-8dupAAGGAGCTGCGGGAGCCG | 5_prime_UTR_variant | Exon 1 of 42 | XP_047297767.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000777 AC: 85AN: 109462Hom.: 0 Cov.: 21 AF XY: 0.000410 AC XY: 13AN XY: 31732
GnomAD3 exomes AF: 0.000184 AC: 32AN: 173882Hom.: 0 AF XY: 0.0000338 AC XY: 2AN XY: 59208
GnomAD4 exome AF: 0.0000565 AC: 60AN: 1062107Hom.: 0 Cov.: 26 AF XY: 0.0000509 AC XY: 17AN XY: 333883
GnomAD4 genome AF: 0.000776 AC: 85AN: 109520Hom.: 0 Cov.: 21 AF XY: 0.000409 AC XY: 13AN XY: 31800
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
This individual is also heterozygous for the c.-25_-8dup18 variant. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This regulatory duplication affects both nonconserved nucleotides and nucleotides conserved through mammals. No regulatory variants have been reported in the Human Gene Mutation Database or observed at GeneDx (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
COL4A5: BS2 -
not specified Uncertain:1
Variant summary: COL4A5 c.-25_-8dup18 is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.00018 in 173882 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in COL4A5 causing Alport Syndrome 1, X-Linked Recessive (0.00018 vs 0.0046), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.-25_-8dup18 in individuals affected with Alport Syndrome 1, X-Linked Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Two submitters classified the variant as VUS while one classified as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. -
X-linked Alport syndrome Uncertain:1
- -
COL4A5-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at