rs4773199
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001846.4(COL4A2):c.4089G>A(p.Ala1363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,587,136 control chromosomes in the GnomAD database, including 39,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.23 ( 4258 hom., cov: 33)
Exomes 𝑓: 0.21 ( 34755 hom. )
Consequence
COL4A2
NM_001846.4 synonymous
NM_001846.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.423
Genes affected
COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. 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, Jul 2008]
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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=-0.74).
BP6
?
Variant 13-110503432-G-A is Benign according to our data. Variant chr13-110503432-G-A is described in ClinVar as [Benign]. Clinvar id is 311171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110503432-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.423 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A2 | NM_001846.4 | c.4089G>A | p.Ala1363= | synonymous_variant | 43/48 | ENST00000360467.7 | |
COL4A2-AS1 | NR_046583.1 | n.187-504C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A2 | ENST00000360467.7 | c.4089G>A | p.Ala1363= | synonymous_variant | 43/48 | 5 | NM_001846.4 | P1 | |
COL4A2-AS1 | ENST00000417970.2 | n.187-504C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
COL4A2 | ENST00000650225.1 | n.1744G>A | non_coding_transcript_exon_variant | 14/19 |
Frequencies
GnomAD3 genomes ? AF: 0.227 AC: 34564AN: 152024Hom.: 4257 Cov.: 33
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GnomAD3 exomes AF: 0.196 AC: 40201AN: 204648Hom.: 4395 AF XY: 0.200 AC XY: 22191AN XY: 110758
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GnomAD4 exome AF: 0.215 AC: 307913AN: 1434994Hom.: 34755 Cov.: 34 AF XY: 0.215 AC XY: 152911AN XY: 711708
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GnomAD4 genome ? AF: 0.227 AC: 34572AN: 152142Hom.: 4258 Cov.: 33 AF XY: 0.220 AC XY: 16350AN XY: 74390
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Porencephaly 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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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