rs1800519
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000092.5(COL4A4):c.2717-5A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,613,524 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000092.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0117 AC: 1784AN: 152174Hom.: 21 Cov.: 33
GnomAD3 exomes AF: 0.0114 AC: 2818AN: 247698Hom.: 30 AF XY: 0.0119 AC XY: 1606AN XY: 134508
GnomAD4 exome AF: 0.0152 AC: 22177AN: 1461232Hom.: 227 Cov.: 31 AF XY: 0.0151 AC XY: 10942AN XY: 726896
GnomAD4 genome AF: 0.0117 AC: 1785AN: 152292Hom.: 21 Cov.: 33 AF XY: 0.0112 AC XY: 833AN XY: 74464
ClinVar
Submissions by phenotype
not provided Benign:6
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COL4A4: BP4, BS1, BS2 -
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This variant is associated with the following publications: (PMID: 15618242) -
not specified Benign:2
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Alport syndrome Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Autosomal recessive Alport syndrome Uncertain:1
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Benign familial hematuria;C5882663:Autosomal dominant Alport syndrome Uncertain:1
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Focal segmental glomerulosclerosis Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at