13-110149715-A-AAT
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001845.6(COL4A1):c.*646_*647dupAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 151,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 0 hom. )
Consequence
COL4A1
NM_001845.6 3_prime_UTR
NM_001845.6 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.41
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 76 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A1 | NM_001845.6 | c.*646_*647dupAT | 3_prime_UTR_variant | Exon 52 of 52 | ENST00000375820.10 | NP_001836.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A1 | ENST00000375820 | c.*646_*647dupAT | 3_prime_UTR_variant | Exon 52 of 52 | 1 | NM_001845.6 | ENSP00000364979.4 | |||
COL4A1 | ENST00000650424 | c.*646_*647dupAT | 3_prime_UTR_variant | Exon 10 of 10 | ENSP00000497477.2 | |||||
COL4A1 | ENST00000649720.1 | n.1824_1825dupAT | non_coding_transcript_exon_variant | Exon 7 of 7 |
Frequencies
GnomAD3 genomes AF: 0.000503 AC: 76AN: 151150Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00228 AC: 1AN: 438Hom.: 0 Cov.: 0 AF XY: 0.00373 AC XY: 1AN XY: 268
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GnomAD4 genome AF: 0.000502 AC: 76AN: 151256Hom.: 0 Cov.: 33 AF XY: 0.000785 AC XY: 58AN XY: 73894
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brain small vessel disease 1 with or without ocular anomalies Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Porencephalic cyst Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at