rs754963967
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_033641.4(COL4A6):āc.604T>Cā(p.Leu202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,207,856 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000063 ( 0 hom., 2 hem., cov: 22)
Exomes š: 0.000044 ( 0 hom. 15 hem. )
Consequence
COL4A6
NM_033641.4 synonymous
NM_033641.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.380
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant X-108206523-A-G is Benign according to our data. Variant chrX-108206523-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 258281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.38 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A6 | NM_033641.4 | c.604T>C | p.Leu202= | synonymous_variant | 9/45 | ENST00000334504.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A6 | ENST00000334504.12 | c.604T>C | p.Leu202= | synonymous_variant | 9/45 | 5 | NM_033641.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000628 AC: 7AN: 111530Hom.: 0 Cov.: 22 AF XY: 0.0000593 AC XY: 2AN XY: 33744
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GnomAD3 exomes AF: 0.000131 AC: 24AN: 182597Hom.: 0 AF XY: 0.000134 AC XY: 9AN XY: 67411
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GnomAD4 exome AF: 0.0000438 AC: 48AN: 1096272Hom.: 0 Cov.: 29 AF XY: 0.0000414 AC XY: 15AN XY: 362058
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GnomAD4 genome ? AF: 0.0000627 AC: 7AN: 111584Hom.: 0 Cov.: 22 AF XY: 0.0000592 AC XY: 2AN XY: 33808
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ClinVar
Significance: Benign/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 | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2023 | - - |
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