chr1-186306378-A-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005807.6(PRG4):c.659A>C(p.Asp220Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,612,992 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0068 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 20 hom. )
Consequence
PRG4
NM_005807.6 missense
NM_005807.6 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 0.520
Genes affected
PRG4 (HGNC:9364): (proteoglycan 4) The protein encoded by this gene is a large proteoglycan that is synthesized by chondrocytes located at the surface of articular cartilage and by some synovial lining cells. This protein contains both chondroitin sulfate and keratan sulfate glycosaminoglycans. It functions as a boundary lubricant at the cartilage surface and contributes to the elastic absorption and energy dissipation of synovial fluid. Mutations in this gene result in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
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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=0.006234437).
BP6
?
Variant 1-186306378-A-C is Benign according to our data. Variant chr1-186306378-A-C is described in ClinVar as [Benign]. Clinvar id is 767737.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00681 (1037/152242) while in subpopulation AFR AF= 0.0224 (931/41518). AF 95% confidence interval is 0.0212. There are 13 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRG4 | NM_005807.6 | c.659A>C | p.Asp220Ala | missense_variant | 7/13 | ENST00000445192.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRG4 | ENST00000445192.7 | c.659A>C | p.Asp220Ala | missense_variant | 7/13 | 5 | NM_005807.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00678 AC: 1031AN: 152124Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.00216 AC: 542AN: 250798Hom.: 7 AF XY: 0.00161 AC XY: 218AN XY: 135508
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GnomAD4 exome AF: 0.000959 AC: 1401AN: 1460750Hom.: 20 Cov.: 31 AF XY: 0.000827 AC XY: 601AN XY: 726630
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GnomAD4 genome ? AF: 0.00681 AC: 1037AN: 152242Hom.: 13 Cov.: 32 AF XY: 0.00668 AC XY: 497AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 08, 2017 | - - |
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;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;.;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;.;D;D;D
Sift4G
Uncertain
D;D;T;D;D;T
Polyphen
0.89, 0.99
.;.;.;P;D;D
Vest4
0.29, 0.27, 0.31, 0.23
MVP
MPC
0.27
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