1-1046551-A-G

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.3066A>G(p.Ser1022Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,610,386 control chromosomes in the GnomAD database, including 647,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 51075 hom., cov: 30)

Exomes 𝑓: 0.90 ( 596839 hom. )

Consequence

AGRN
NM_198576.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.03

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=-0.97).

BP6

Variant 1-1046551-A-G is Benign according to our data. Variant chr1-1046551-A-G is described in ClinVar as [Benign]. Clinvar id is 128297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-1046551-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.3066A>G	p.Ser1022Ser	synonymous_variant	Exon 18 of 36	ENST00000379370.7	NP_940978.2	O00468-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGRN	ENST00000379370.7 link	c.3066A>G	p.Ser1022Ser	synonymous_variant	Exon 18 of 36	1	NM_198576.4	ENSP00000368678.2		O00468-6

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121546

AN:

151638

Hom.:

51078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.986

Gnomad AMR

AF:

0.881

Gnomad ASJ

AF:

0.893

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.892

Gnomad FIN

AF:

0.936

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.824

GnomAD3 exomes

AF:

0.887

AC:

216630

AN:

244354

Hom.:

97400

AF XY:

0.891

AC XY:

118804

AN XY:

133338

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.930

Gnomad ASJ exome

AF:

0.888

Gnomad EAS exome

AF:

0.968

Gnomad SAS exome

AF:

0.888

Gnomad FIN exome

AF:

0.932

Gnomad NFE exome

AF:

0.906

Gnomad OTH exome

AF:

0.884

GnomAD4 exome

AF:

0.902

AC:

1315696

AN:

1458630

Hom.:

596839

Cov.:

AF XY:

0.902

AC XY:

654709

AN XY:

725646

show subpopulations

Gnomad4 AFR exome

AF:

0.488

Gnomad4 AMR exome

AF:

0.923

Gnomad4 ASJ exome

AF:

0.886

Gnomad4 EAS exome

AF:

0.967

Gnomad4 SAS exome

AF:

0.887

Gnomad4 FIN exome

AF:

0.929

Gnomad4 NFE exome

AF:

0.913

Gnomad4 OTH exome

AF:

0.881

GnomAD4 genome

AF:

0.801

AC:

121566

AN:

151756

Hom.:

51075

Cov.:

AF XY:

0.805

AC XY:

59735

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.513

Gnomad4 AMR

AF:

0.881

Gnomad4 ASJ

AF:

0.893

Gnomad4 EAS

AF:

0.962

Gnomad4 SAS

AF:

0.891

Gnomad4 FIN

AF:

0.936

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.826

Alfa

AF:

0.881

Hom.:

18957

Bravo

AF:

0.783

Asia WGS

AF:

0.903

AC:

3142

AN:

3478

EpiCase

AF:

0.902

EpiControl

AF:

0.897

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 19, 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. -

Congenital myasthenic syndrome 8

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.12

DANN

Benign

0.19

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