rs139886237
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_198576.4(AGRN):c.2067G>A(p.Gln689=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,613,266 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0037 ( 22 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.33
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=-0.53).
BP6
?
Variant 1-1044176-G-A is Benign according to our data. Variant chr1-1044176-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.33 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00284 (432/152322) while in subpopulation NFE AF= 0.0045 (306/68018). AF 95% confidence interval is 0.00408. There are 0 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.2067G>A | p.Gln689= | synonymous_variant | 11/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.2067G>A | p.Gln689= | synonymous_variant | 11/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.1752G>A | p.Gln584= | synonymous_variant | 10/38 | ||||
AGRN | ENST00000652369.1 | c.1752G>A | p.Gln584= | synonymous_variant | 10/35 | ||||
AGRN | ENST00000620552.4 | c.1653G>A | p.Gln551= | synonymous_variant | 11/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00284 AC: 432AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00290 AC: 725AN: 250430Hom.: 3 AF XY: 0.00294 AC XY: 399AN XY: 135712
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GnomAD4 exome AF: 0.00370 AC: 5402AN: 1460944Hom.: 22 Cov.: 35 AF XY: 0.00354 AC XY: 2574AN XY: 726824
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GnomAD4 genome ? AF: 0.00284 AC: 432AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.00243 AC XY: 181AN XY: 74496
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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 provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | AGRN: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 20, 2019 | - - |
AGRN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 08, 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). - |
Congenital myasthenic syndrome 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at