chr9-98985603-A-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001855.5(COL15A1):āc.139A>Gā(p.Ile47Val) variant causes a missense change. The variant allele was found at a frequency of 0.00254 in 1,614,180 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.013 ( 50 hom., cov: 33)
Exomes š: 0.0014 ( 48 hom. )
Consequence
COL15A1
NM_001855.5 missense
NM_001855.5 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 3.76
Genes affected
COL15A1 (HGNC:2192): (collagen type XV alpha 1 chain) This gene encodes the alpha chain of type XV collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Type XV collagen has a wide tissue distribution but the strongest expression is localized to basement membrane zones so it may function to adhere basement membranes to underlying connective tissue stroma. The proteolytically produced C-terminal fragment of type XV collagen is restin, a potentially antiangiogenic protein that is closely related to endostatin. Mouse studies have shown that collagen XV deficiency is associated with muscle and microvessel deterioration. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.005355954).
BP6
Variant 9-98985603-A-G is Benign according to our data. Variant chr9-98985603-A-G is described in ClinVar as [Benign]. Clinvar id is 3056690.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2043/152352) while in subpopulation AFR AF= 0.047 (1952/41570). AF 95% confidence interval is 0.0452. There are 50 homozygotes in gnomad4. There are 950 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 50 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL15A1 | NM_001855.5 | c.139A>G | p.Ile47Val | missense_variant | 3/42 | ENST00000375001.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL15A1 | ENST00000375001.8 | c.139A>G | p.Ile47Val | missense_variant | 3/42 | 1 | NM_001855.5 | P1 | |
COL15A1 | ENST00000471477.1 | n.562A>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0134 AC: 2037AN: 152234Hom.: 50 Cov.: 33
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GnomAD3 exomes AF: 0.00355 AC: 891AN: 251074Hom.: 19 AF XY: 0.00254 AC XY: 344AN XY: 135696
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GnomAD4 exome AF: 0.00140 AC: 2052AN: 1461828Hom.: 48 Cov.: 31 AF XY: 0.00126 AC XY: 917AN XY: 727200
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GnomAD4 genome AF: 0.0134 AC: 2043AN: 152352Hom.: 50 Cov.: 33 AF XY: 0.0128 AC XY: 950AN XY: 74506
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
COL15A1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 12, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at