rs111945121
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000092.5(COL4A4):c.666G>T(p.Pro222=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P222P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
COL4A4
NM_000092.5 synonymous
NM_000092.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.41
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 2-227108860-C-A is Benign according to our data. Variant chr2-227108860-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 765328.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.41 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A4 | NM_000092.5 | c.666G>T | p.Pro222= | synonymous_variant | 11/48 | ENST00000396625.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A4 | ENST00000396625.5 | c.666G>T | p.Pro222= | synonymous_variant | 11/48 | 5 | NM_000092.5 | P1 | |
COL4A4 | ENST00000643379.1 | c.666G>T | p.Pro222= | synonymous_variant | 11/15 | ||||
COL4A4 | ENST00000682248.1 | n.767G>T | non_coding_transcript_exon_variant | 10/11 | |||||
COL4A4 | ENST00000684257.1 | n.620G>T | non_coding_transcript_exon_variant | 9/10 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1459540Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 725892
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1459540
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
725892
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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