rs373058941

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_198576.4(AGRN):c.5370+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,557,644 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00098 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.92

Publications

0 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-1051380-G-A is Benign according to our data. Variant chr1-1051380-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 263198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.5370+11G>A		intron_variant	Intron 31 of 35	ENST00000379370.7	NP_940978.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
AGRN	ENST00000379370.7 link	c.5370+11G>A	intron_variant	Intron 31 of 35	1	NM_198576.4	ENSP00000368678.2
AGRN	ENST00000651234.1 link	c.5067+11G>A	intron_variant	Intron 31 of 37			ENSP00000499046.1
AGRN	ENST00000652369.2 link	c.5055+11G>A	intron_variant	Intron 30 of 34			ENSP00000498543.1
AGRN	ENST00000620552.4 link	c.4968+11G>A	intron_variant	Intron 32 of 38	5		ENSP00000484607.1

Frequencies

GnomAD3 genomes

AF:

0.000980

AC:

149

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000907

AC:

144

AN:

158752

AF XY:

0.000874

show subpopulations

Gnomad AFR exome

AF:

0.000440

Gnomad AMR exome

AF:

0.000391

Gnomad ASJ exome

AF:

0.000956

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000245

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.000452

GnomAD4 exome

AF:

0.00149

AC:

2088

AN:

1405412

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1014

AN XY:

694324

show subpopulations

African (AFR)

AF:

0.0000921

AC:

AN:

32564

American (AMR)

AF:

0.000406

AC:

AN:

36902

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

25204

East Asian (EAS)

AF:

0.00

AC:

AN:

37440

South Asian (SAS)

AF:

0.000212

AC:

AN:

80248

European-Finnish (FIN)

AF:

0.000224

AC:

AN:

44592

Middle Eastern (MID)

AF:

0.000785

AC:

AN:

5094

European-Non Finnish (NFE)

AF:

0.00178

AC:

1935

AN:

1085042

Other (OTH)

AF:

0.00132

AC:

AN:

58326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

131

262

393

524

655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.000979

AC:

149

AN:

152232

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41538

American (AMR)

AF:

0.000523

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00179

AC:

122

AN:

67976

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00115

Hom.:

Bravo

AF:

0.00110

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 13, 2016

GeneDx

Significance:Likely 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. -

Congenital myasthenic syndrome 8

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.2

(source)

DANN

Benign

0.82

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over