rs28484890
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_198576.4(AGRN):c.2025C>G(p.Gly675=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,270 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 29 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 30 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.405
Genes affected
AGRN (HGNC:329): (agrin) This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 1-1044134-C-G is Benign according to our data. Variant chr1-1044134-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 128293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.405 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1585/152318) while in subpopulation AFR AF= 0.0362 (1504/41568). AF 95% confidence interval is 0.0347. There are 29 homozygotes in gnomad4. There are 753 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 28 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.2025C>G | p.Gly675= | synonymous_variant | 11/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.2025C>G | p.Gly675= | synonymous_variant | 11/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.1710C>G | p.Gly570= | synonymous_variant | 10/38 | ||||
AGRN | ENST00000652369.1 | c.1710C>G | p.Gly570= | synonymous_variant | 10/35 | ||||
AGRN | ENST00000620552.4 | c.1611C>G | p.Gly537= | synonymous_variant | 11/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0103 AC: 1569AN: 152200Hom.: 28 Cov.: 33
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GnomAD3 exomes AF: 0.00280 AC: 700AN: 250268Hom.: 12 AF XY: 0.00213 AC XY: 289AN XY: 135678
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GnomAD4 exome AF: 0.00113 AC: 1646AN: 1460952Hom.: 30 Cov.: 35 AF XY: 0.000967 AC XY: 703AN XY: 726818
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GnomAD4 genome ? AF: 0.0104 AC: 1585AN: 152318Hom.: 29 Cov.: 33 AF XY: 0.0101 AC XY: 753AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 2020 | - - |
Congenital myasthenic syndrome 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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