rs17160781

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198576.4(AGRN):c.5358T>C(p.Gly1786Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,552,364 control chromosomes in the GnomAD database, including 2,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 1277 hom., cov: 33)

Exomes 𝑓: 0.014 ( 1190 hom. )

Consequence

AGRN
NM_198576.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.595

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-1051357-T-C is Benign according to our data. Variant chr1-1051357-T-C is described in ClinVar as [Benign]. Clinvar id is 128315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.595 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.5358T>C	p.Gly1786Gly	synonymous_variant	Exon 31 of 36	ENST00000379370.7	NP_940978.2	O00468-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGRN	ENST00000379370.7 link	c.5358T>C	p.Gly1786Gly	synonymous_variant	Exon 31 of 36	1	NM_198576.4	ENSP00000368678.2	O00468-6
AGRN	ENST00000651234.1 link	c.5055T>C	p.Gly1685Gly	synonymous_variant	Exon 31 of 38			ENSP00000499046.1	A0A494C1I6
AGRN	ENST00000652369.1 link	c.5043T>C	p.Gly1681Gly	synonymous_variant	Exon 30 of 35			ENSP00000498543.1	A0A494C0G5
AGRN	ENST00000620552.4 link	c.4956T>C	p.Gly1652Gly	synonymous_variant	Exon 32 of 39	5		ENSP00000484607.1	A0A087X208

Frequencies

GnomAD3 genomes

AF:

0.0771

AC:

11472

AN:

148830

Hom.:

1260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.00673

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.00322

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00569

Gnomad FIN

AF:

0.000719

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00861

Gnomad OTH

AF:

0.0632

GnomAD3 exomes

AF:

0.0221

AC:

3775

AN:

170702

Hom.:

309

AF XY:

0.0178

AC XY:

1636

AN XY:

91718

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.00364

Gnomad EAS exome

AF:

0.0000741

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00861

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0138

AC:

19319

AN:

1403408

Hom.:

1190

Cov.:

AF XY:

0.0128

AC XY:

8900

AN XY:

693778

show subpopulations

Gnomad4 AFR exome

AF:

0.256

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.00377

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00396

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00751

Gnomad4 OTH exome

AF:

0.0253

GnomAD4 genome

AF:

0.0774

AC:

11534

AN:

148956

Hom.:

1277

Cov.:

AF XY:

0.0743

AC XY:

5406

AN XY:

72718

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.00322

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00569

Gnomad4 FIN

AF:

0.000719

Gnomad4 NFE

AF:

0.00861

Gnomad4 OTH

AF:

0.0625

Alfa

AF:

0.0375

Hom.:

314

Bravo

AF:

0.0864

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 29, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 20, 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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.12

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over