chrX-108666560-T-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_033380.3(COL4A5):āc.3519T>Gā(p.Gly1173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00577 in 1,206,410 control chromosomes in the GnomAD database, including 242 homozygotes. There are 1,861 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.030 ( 120 hom., 910 hem., cov: 22)
Exomes š: 0.0033 ( 122 hom. 951 hem. )
Consequence
COL4A5
NM_033380.3 synonymous
NM_033380.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.151
Genes affected
COL4A5 (HGNC:2207): (collagen type IV alpha 5 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]
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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=-0.47).
BP6
Variant X-108666560-T-G is Benign according to our data. Variant chrX-108666560-T-G is described in ClinVar as [Benign]. Clinvar id is 256280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108666560-T-G is described in Lovd as [Benign]. Variant chrX-108666560-T-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.151 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.3519T>G | p.Gly1173= | synonymous_variant | 39/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.3519T>G | p.Gly1173= | synonymous_variant | 39/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000361603.7 | c.3519T>G | p.Gly1173= | synonymous_variant | 39/51 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0300 AC: 3364AN: 112134Hom.: 120 Cov.: 22 AF XY: 0.0263 AC XY: 902AN XY: 34290
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GnomAD3 exomes AF: 0.00888 AC: 1542AN: 173623Hom.: 57 AF XY: 0.00549 AC XY: 326AN XY: 59331
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GnomAD4 exome AF: 0.00328 AC: 3587AN: 1094222Hom.: 122 Cov.: 30 AF XY: 0.00264 AC XY: 951AN XY: 360102
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GnomAD4 genome AF: 0.0301 AC: 3375AN: 112188Hom.: 120 Cov.: 22 AF XY: 0.0265 AC XY: 910AN XY: 34354
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 23, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 18, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
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 | p.Gly1173Gly in exon 39 of COL4A5: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 12.25% (794/6480) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs61735627). - |
Kidney disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 16, 2021 | - - |
X-linked Alport syndrome Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
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