chr2-227059469-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000092.5(COL4A4):c.2319G>A(p.Arg773Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000072 ( 0 hom. )
Consequence
COL4A4
NM_000092.5 synonymous
NM_000092.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.21
Genes affected
COL4A4 (HGNC:2206): (collagen type IV alpha 4 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. 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. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 2-227059469-C-T is Benign according to our data. Variant chr2-227059469-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 517581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.21 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A4 | NM_000092.5 | c.2319G>A | p.Arg773Arg | synonymous_variant | 28/48 | ENST00000396625.5 | NP_000083.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A4 | ENST00000396625.5 | c.2319G>A | p.Arg773Arg | synonymous_variant | 28/48 | 5 | NM_000092.5 | ENSP00000379866.3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152114Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000132 AC: 33AN: 249564Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 135396
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GnomAD4 exome AF: 0.0000718 AC: 105AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000990 AC XY: 72AN XY: 727242
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152234Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 4AN XY: 74426
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 14, 2017 | p.Arg773Arg in exon 28 of COL4A4: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.1% (33/30778) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org; dbSNP rs200920187). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at