NM_000393.5:c.370-16C>T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000393.5(COL5A2):c.370-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 1,609,678 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000393.5 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.370-16C>T | intron_variant | Intron 4 of 53 | ENST00000374866.9 | NP_000384.2 | ||
COL5A2 | XM_011510573.4 | c.232-16C>T | intron_variant | Intron 7 of 56 | XP_011508875.1 | |||
COL5A2 | XM_047443251.1 | c.232-16C>T | intron_variant | Intron 9 of 58 | XP_047299207.1 | |||
COL5A2 | XM_047443252.1 | c.232-16C>T | intron_variant | Intron 8 of 57 | XP_047299208.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.370-16C>T | intron_variant | Intron 4 of 53 | 1 | NM_000393.5 | ENSP00000364000.3 | |||
COL5A2 | ENST00000618828.1 | c.-261-16C>T | intron_variant | Intron 4 of 46 | 5 | ENSP00000482184.1 | ||||
COL5A2 | ENST00000649966.1 | c.232-16C>T | intron_variant | Intron 4 of 10 | ENSP00000496785.1 |
Frequencies
GnomAD3 genomes AF: 0.00732 AC: 1114AN: 152136Hom.: 8 Cov.: 33
GnomAD3 exomes AF: 0.00737 AC: 1848AN: 250852Hom.: 11 AF XY: 0.00719 AC XY: 975AN XY: 135624
GnomAD4 exome AF: 0.00755 AC: 11003AN: 1457424Hom.: 70 Cov.: 28 AF XY: 0.00739 AC XY: 5363AN XY: 725314
GnomAD4 genome AF: 0.00730 AC: 1112AN: 152254Hom.: 8 Cov.: 33 AF XY: 0.00702 AC XY: 523AN XY: 74452
ClinVar
Submissions by phenotype
not specified Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:2
Variant summary: The COL5A2 c.370-16C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing while ESE finder predicts the loss of a SRp40 binding motif. However, these predictions have yet to be confirmed by functional studies. The variant of interest has been observed in a large, broad control population, ExAC, in 762/119346 control chromosomes (2 homozygotes) at a frequency of 0.0063848, which is approximately 1022 times the estimated maximal expected allele frequency of a pathogenic COL5A2 variant (0.0000063), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
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Ehlers-Danlos syndrome, classic type, 2 Benign:1
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Ehlers-Danlos syndrome, classic type 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