rs10492497
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001845.6(COL4A1):c.2194-98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,537,726 control chromosomes in the GnomAD database, including 4,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.076 ( 437 hom., cov: 33)
Exomes 𝑓: 0.075 ( 4251 hom. )
Consequence
COL4A1
NM_001845.6 intron
NM_001845.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.40
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 13-110179519-T-C is Benign according to our data. Variant chr13-110179519-T-C is described in ClinVar as [Benign]. Clinvar id is 1293322.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110179519-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A1 | NM_001845.6 | c.2194-98A>G | intron_variant | ENST00000375820.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A1 | ENST00000375820.10 | c.2194-98A>G | intron_variant | 1 | NM_001845.6 | P1 | |||
COL4A1 | ENST00000649738.1 | n.2324-98A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0759 AC: 11558AN: 152180Hom.: 437 Cov.: 33
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GnomAD4 exome AF: 0.0752 AC: 104134AN: 1385428Hom.: 4251 AF XY: 0.0744 AC XY: 51587AN XY: 693370
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GnomAD4 genome ? AF: 0.0760 AC: 11570AN: 152298Hom.: 437 Cov.: 33 AF XY: 0.0777 AC XY: 5783AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
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