rs104886089
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_033380.3(COL4A5):c.1033-15delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,093,951 control chromosomes in the GnomAD database, including 15 homozygotes. There are 1,338 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Consequence
NM_033380.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.1033-24delT | intron_variant | Intron 18 of 52 | 1 | NM_033380.3 | ENSP00000331902.7 | |||
COL4A5 | ENST00000483338.1 | c.-144-24delT | intron_variant | Intron 2 of 19 | 1 | ENSP00000495685.1 | ||||
COL4A5 | ENST00000361603.7 | c.1033-24delT | intron_variant | Intron 18 of 50 | 2 | ENSP00000354505.2 |
Frequencies
GnomAD3 genomes AF: 0.00446 AC: 474AN: 106330Hom.: 4 Cov.: 21 AF XY: 0.00429 AC XY: 129AN XY: 30088
GnomAD3 exomes AF: 0.00681 AC: 911AN: 133794Hom.: 5 AF XY: 0.00698 AC XY: 301AN XY: 43100
GnomAD4 exome AF: 0.00410 AC: 4046AN: 987588Hom.: 11 Cov.: 26 AF XY: 0.00383 AC XY: 1209AN XY: 315924
GnomAD4 genome AF: 0.00446 AC: 474AN: 106363Hom.: 4 Cov.: 21 AF XY: 0.00428 AC XY: 129AN XY: 30135
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: COL4A5 c.1033-15delT alters a non-conserved nucleotide within a poly-T region located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0068 in 133794 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 1.5-fold of the estimated maximal expected allele frequency for a pathogenic variant in COL4A5 causing Alport Syndrome 1, X-Linked Recessive phenotype (0.0046), strongly suggesting that the variant is benign. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:1
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X-linked Alport syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at