rs55928538
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000091.5(COL4A3):c.933+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 1,612,948 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 54 hom., cov: 33)
Exomes 𝑓: 0.032 ( 814 hom. )
Consequence
COL4A3
NM_000091.5 intron
NM_000091.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0190
Genes affected
COL4A3 (HGNC:2204): (collagen type IV alpha 3 chain) Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3. In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein. A specific kinase phosphorylates amino acids in this same C-terminal region and the expression of this kinase is upregulated during pathogenesis. This gene is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to this syndrome are also located within the exons that encode this C-terminal region. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 2-227256084-T-C is Benign according to our data. Variant chr2-227256084-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-227256084-T-C is described in Lovd as [Benign].
BA1
?
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A3 | NM_000091.5 | c.933+14T>C | intron_variant | ENST00000396578.8 | |||
MFF-DT | NR_102371.1 | n.1592+3094A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A3 | ENST00000396578.8 | c.933+14T>C | intron_variant | 1 | NM_000091.5 | P1 | |||
MFF-DT | ENST00000439598.6 | n.1592+3094A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0242 AC: 3678AN: 152210Hom.: 54 Cov.: 33
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GnomAD3 exomes AF: 0.0270 AC: 6739AN: 249404Hom.: 136 AF XY: 0.0286 AC XY: 3873AN XY: 135318
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GnomAD4 exome AF: 0.0316 AC: 46118AN: 1460620Hom.: 814 Cov.: 30 AF XY: 0.0318 AC XY: 23107AN XY: 726718
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GnomAD4 genome ? AF: 0.0241 AC: 3678AN: 152328Hom.: 54 Cov.: 33 AF XY: 0.0240 AC XY: 1784AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | c.933+14T>C in intron 16 of COL4A3: This variant is not expected to have clinica l significance because it is not located within the splice consensus sequence an d has been identified in 3.58% (2388/66624) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs55928538) . - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Autosomal recessive Alport syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Alport syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
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