chr13-110187165-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001845.6(COL4A1):c.1701G>A(p.Pro567=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,614,002 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 3 hom. )
Consequence
COL4A1
NM_001845.6 synonymous
NM_001845.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.28
Genes affected
COL4A1 (HGNC:2202): (collagen type IV alpha 1 chain) This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
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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=-0.58).
BP6
?
Variant 13-110187165-C-T is Benign according to our data. Variant chr13-110187165-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 585511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110187165-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.28 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00414 (631/152312) while in subpopulation AFR AF= 0.0145 (602/41568). AF 95% confidence interval is 0.0135. There are 7 homozygotes in gnomad4. There are 279 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 623 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A1 | NM_001845.6 | c.1701G>A | p.Pro567= | synonymous_variant | 25/52 | ENST00000375820.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A1 | ENST00000375820.10 | c.1701G>A | p.Pro567= | synonymous_variant | 25/52 | 1 | NM_001845.6 | P1 | |
COL4A1 | ENST00000649738.1 | n.1831G>A | non_coding_transcript_exon_variant | 25/31 |
Frequencies
GnomAD3 genomes ? AF: 0.00409 AC: 623AN: 152194Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.000979 AC: 246AN: 251298Hom.: 0 AF XY: 0.000766 AC XY: 104AN XY: 135838
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GnomAD4 exome AF: 0.000425 AC: 621AN: 1461690Hom.: 3 Cov.: 32 AF XY: 0.000395 AC XY: 287AN XY: 727142
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 20, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | COL4A1: BP4, BP7, BS1, BS2 - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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