rs113020870
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_198576.4(AGRN):c.4839C>T(p.Cys1613Cys) 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 -16 ACMG points.
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.
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. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 21 AR gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.4839C>T | p.Cys1613Cys | synonymous_variant | 27/36 | 1 | NM_198576.4 | ENSP00000368678.2 | ||
AGRN | ENST00000651234.1 | c.4524C>T | p.Cys1508Cys | synonymous_variant | 26/38 | ENSP00000499046.1 | ||||
AGRN | ENST00000652369.1 | c.4524C>T | p.Cys1508Cys | synonymous_variant | 26/35 | ENSP00000498543.1 | ||||
AGRN | ENST00000620552.4 | c.4425C>T | p.Cys1475Cys | synonymous_variant | 27/39 | 5 | ENSP00000484607.1 |
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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GnomAD4 genome AF: 0.00296 AC: 429AN: 144898Hom.: 0 Cov.: 33 AF XY: 0.00300 AC XY: 212AN XY: 70584
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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
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 27, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | AGRN: PP3, BS2 - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 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
DS_DG_spliceai
Position offset: -2
DS_DL_spliceai
Position offset: 40
Find out detailed SpliceAI scores and Pangolin per-transcript scores at