rs200333878
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000093.5(COL5A1):c.3906+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,550,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_000093.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.3906+7G>A | splice_region_variant, intron_variant | Intron 49 of 65 | ENST00000371817.8 | NP_000084.3 | ||
COL5A1 | NM_001278074.1 | c.3906+7G>A | splice_region_variant, intron_variant | Intron 49 of 65 | NP_001265003.1 | |||
COL5A1 | XM_017014266.3 | c.3906+7G>A | splice_region_variant, intron_variant | Intron 49 of 64 | XP_016869755.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3906+7G>A | splice_region_variant, intron_variant | Intron 49 of 65 | 1 | NM_000093.5 | ENSP00000360882.3 | |||
COL5A1 | ENST00000371820.4 | c.3906+7G>A | splice_region_variant, intron_variant | Intron 49 of 65 | 2 | ENSP00000360885.4 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000259 AC: 4AN: 154546Hom.: 0 AF XY: 0.0000244 AC XY: 2AN XY: 81818
GnomAD4 exome AF: 0.0000508 AC: 71AN: 1398328Hom.: 0 Cov.: 32 AF XY: 0.0000391 AC XY: 27AN XY: 689726
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152342Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4AN XY: 74504
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: COL5A1 c.3906+7G>A alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predicts 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 4.9e-05 in 1543766 control chromosomes in the gnomAD database (v4.1 dataset). The observed variant frequency is approximately 1.6-fold of the estimated maximal expected allele frequency for a pathogenic variant in COL5A1 causing Ehlers-Danlos Syndrome phenotype (3.1e-05). To our knowledge, no occurrence of c.3906+7G>A in individuals affected with Ehlers-Danlos Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 529297). Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:1
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Ehlers-Danlos syndrome, classic type, 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at