rs113020870
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_198576.4(AGRN):c.4839C>T(p.Cys1613=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,513,062 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0044 ( 21 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.325
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=-0.52).
BP6
?
Variant 1-1049997-C-T is Benign according to our data. Variant chr1-1049997-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 263189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.325 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00296 (429/144898) while in subpopulation NFE AF= 0.00435 (288/66144). AF 95% confidence interval is 0.00394. There are 0 homozygotes in gnomad4. There are 212 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.4839C>T | p.Cys1613= | synonymous_variant | 27/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.4839C>T | p.Cys1613= | synonymous_variant | 27/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.4524C>T | p.Cys1508= | synonymous_variant | 26/38 | ||||
AGRN | ENST00000652369.1 | c.4524C>T | p.Cys1508= | synonymous_variant | 26/35 | ||||
AGRN | ENST00000620552.4 | c.4425C>T | p.Cys1475= | synonymous_variant | 27/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00296 AC: 429AN: 144784Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00273 AC: 647AN: 237116Hom.: 2 AF XY: 0.00268 AC XY: 350AN XY: 130706
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GnomAD4 exome AF: 0.00436 AC: 5961AN: 1368164Hom.: 21 Cov.: 72 AF XY: 0.00420 AC XY: 2856AN XY: 680044
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | AGRN: PP3, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 27, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Congenital myasthenic syndrome 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
Cadd
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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
DS_DG_spliceai
Position offset: -2
DS_DL_spliceai
Position offset: 40
Find out detailed SpliceAI scores and Pangolin per-transcript scores at