rs114389542

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198576.4(AGRN):c.2254+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00735 in 1,597,636 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 85 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 127 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.288

Publications

2 publications found

Variant links:

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]

AGRN Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 8
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AGRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-1044455-G-A is Benign according to our data. Variant chr1-1044455-G-A is described in ClinVar as Benign. ClinVar VariationId is 263168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AGRN	NM_198576.4	MANE Select	c.2254+16G>A	intron	N/A	NP_940978.2
AGRN	NM_001305275.2		c.2254+16G>A	intron	N/A	NP_001292204.1
AGRN	NM_001364727.2		c.1939+16G>A	intron	N/A	NP_001351656.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AGRN	ENST00000379370.7	TSL:1 MANE Select	c.2254+16G>A	intron	N/A	ENSP00000368678.2
AGRN	ENST00000651234.1		c.1939+16G>A	intron	N/A	ENSP00000499046.1
AGRN	ENST00000652369.2		c.1939+16G>A	intron	N/A	ENSP00000498543.1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3391

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.0317

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0114

AC:

2459

AN:

216482

AF XY:

0.0106

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.00612

Gnomad EAS exome

AF:

0.0271

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00948

GnomAD4 exome

AF:

0.00577

AC:

8335

AN:

1445298

Hom.:

127

Cov.:

AF XY:

0.00566

AC XY:

4065

AN XY:

717890

show subpopulations

African (AFR)

AF:

0.0651

AC:

2149

AN:

33008

American (AMR)

AF:

0.00646

AC:

273

AN:

42246

Ashkenazi Jewish (ASJ)

AF:

0.00557

AC:

144

AN:

25874

East Asian (EAS)

AF:

0.0295

AC:

1137

AN:

38532

South Asian (SAS)

AF:

0.00913

AC:

772

AN:

84594

European-Finnish (FIN)

AF:

0.0183

AC:

932

AN:

50936

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.00208

AC:

2302

AN:

1104770

Other (OTH)

AF:

0.00951

AC:

568

AN:

59714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

493

987

1480

1974

2467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0223

AC:

3403

AN:

152338

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1720

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0628

AC:

2609

AN:

41566

American (AMR)

AF:

0.0114

AC:

174

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3466

East Asian (EAS)

AF:

0.0316

AC:

164

AN:

5192

South Asian (SAS)

AF:

0.0101

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0190

AC:

202

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00245

AC:

167

AN:

68034

Other (OTH)

AF:

0.0114

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

157

313

470

626

783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00672

Hom.:

Bravo

AF:

0.0227

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 31, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Congenital myasthenic syndrome 8

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.44

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over