rs767901025
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000092.5(COL4A4):c.4817G>A(p.Gly1606Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,452 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000092.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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COL4A4 | ENST00000396625.5 | c.4817G>A | p.Gly1606Glu | missense_variant | Exon 48 of 48 | 5 | NM_000092.5 | ENSP00000379866.3 | ||
COL4A4 | ENST00000682098.1 | c.419G>A | p.Gly140Glu | missense_variant | Exon 3 of 3 | ENSP00000508331.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000364 AC: 9AN: 247394Hom.: 0 AF XY: 0.0000521 AC XY: 7AN XY: 134436
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460124Hom.: 0 Cov.: 35 AF XY: 0.0000138 AC XY: 10AN XY: 726358
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74474
ClinVar
Submissions by phenotype
Autosomal recessive Alport syndrome Uncertain:2
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.72; 3Cnet: 0.02). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -
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Autosomal recessive Alport syndrome;CN376803:Hematuria, benign familial, 1 Pathogenic:1
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at