rs617111
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1BS2_Supporting
The NM_001845.6(COL4A1):c.4641-32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,555,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
COL4A1
NM_001845.6 intron
NM_001845.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.89
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000328 (5/152278) while in subpopulation EAS AF= 0.000967 (5/5170). AF 95% confidence interval is 0.000381. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A1 | NM_001845.6 | c.4641-32G>C | intron_variant | ENST00000375820.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A1 | ENST00000375820.10 | c.4641-32G>C | intron_variant | 1 | NM_001845.6 | P1 | |||
COL4A1 | ENST00000650424.1 | c.797-32G>C | intron_variant | ||||||
COL4A1 | ENST00000649720.1 | n.809-32G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152160Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000836 AC: 2AN: 239142Hom.: 0 AF XY: 0.00000773 AC XY: 1AN XY: 129424
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GnomAD4 exome AF: 0.00000214 AC: 3AN: 1402774Hom.: 0 Cov.: 23 AF XY: 0.00000143 AC XY: 1AN XY: 700594
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74470
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ClinVar
Not reported inComputational scores
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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