rs2295912
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_033641.4(COL4A6):c.3402C>T(p.Ala1134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,204,103 control chromosomes in the GnomAD database, including 600 homozygotes. There are 11,102 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.051 ( 207 hom., 1616 hem., cov: 24)
Exomes 𝑓: 0.027 ( 393 hom. 9486 hem. )
Consequence
COL4A6
NM_033641.4 synonymous
NM_033641.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0930
Genes affected
COL4A6 (HGNC:2208): (collagen type IV alpha 6 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component 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, alpha 5 type IV collagen, so that the gene pair shares a common promoter. Deletions in the alpha 5 gene that extend into the alpha 6 gene result in diffuse leiomyomatosis accompanying the X-linked Alport syndrome caused by the deletion in the alpha 5 gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]
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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=-0.78).
BP6
?
Variant X-108170700-G-A is Benign according to our data. Variant chrX-108170700-G-A is described in ClinVar as [Benign]. Clinvar id is 258274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.093 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A6 | NM_033641.4 | c.3402C>T | p.Ala1134= | synonymous_variant | 35/45 | ENST00000334504.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A6 | ENST00000334504.12 | c.3402C>T | p.Ala1134= | synonymous_variant | 35/45 | 5 | NM_033641.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0508 AC: 5683AN: 111817Hom.: 206 Cov.: 24 AF XY: 0.0473 AC XY: 1609AN XY: 34015
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GnomAD3 exomes AF: 0.0365 AC: 6480AN: 177302Hom.: 154 AF XY: 0.0334 AC XY: 2099AN XY: 62782
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GnomAD4 exome AF: 0.0265 AC: 28952AN: 1092231Hom.: 393 Cov.: 30 AF XY: 0.0264 AC XY: 9486AN XY: 358957
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GnomAD4 genome ? AF: 0.0508 AC: 5688AN: 111872Hom.: 207 Cov.: 24 AF XY: 0.0474 AC XY: 1616AN XY: 34080
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ClinVar
Significance: Benign
Submissions summary: Benign:5
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 | GeneDx | May 09, 2017 | 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 12, 2018 | - - |
Hearing loss, X-linked 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
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