Variant rs3128098 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000379370.7(AGRN):c.2537-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,613,008 control chromosomes in the GnomAD database, including 683,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.85 ( 56745 hom., cov: 34)

Exomes 𝑓: 0.93 ( 627219 hom. )

Consequence

AGRN
ENST00000379370.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.863

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-1045707-A-G is Benign according to our data. Variant chr1-1045707-A-G is described in ClinVar as [Benign]. Clinvar id is 263172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGRN	NM_198576.4 linkuse as main transcript	c.2537-26A>G		intron_variant		ENST00000379370.7	NP_940978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGRN	ENST00000379370.7 linkuse as main transcript	c.2537-26A>G		intron_variant		1	NM_198576.4	ENSP00000368678	P1	O00468-6

Frequencies

GnomAD3 genomes

AF:

0.854

AC:

129873

AN:

152106

Hom.:

56727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.992

Gnomad AMR

AF:

0.910

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.962

Gnomad FIN

AF:

0.960

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.928

Gnomad OTH

AF:

0.868

GnomAD3 exomes

AF:

0.921

AC:

229847

AN:

249684

Hom.:

106599

AF XY:

0.926

AC XY:

125362

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.946

Gnomad ASJ exome

AF:

0.919

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.955

Gnomad FIN exome

AF:

0.956

Gnomad NFE exome

AF:

0.925

Gnomad OTH exome

AF:

0.916

GnomAD4 exome

AF:

0.925

AC:

1351529

AN:

1460784

Hom.:

627219

Cov.:

AF XY:

0.927

AC XY:

673516

AN XY:

726710

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.941

Gnomad4 ASJ exome

AF:

0.917

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.956

Gnomad4 FIN exome

AF:

0.953

Gnomad4 NFE exome

AF:

0.928

Gnomad4 OTH exome

AF:

0.914

GnomAD4 genome

AF:

0.854

AC:

129943

AN:

152224

Hom.:

56745

Cov.:

AF XY:

0.858

AC XY:

63865

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.911

Gnomad4 ASJ

AF:

0.916

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.961

Gnomad4 FIN

AF:

0.960

Gnomad4 NFE

AF:

0.928

Gnomad4 OTH

AF:

0.870

Alfa

AF:

0.896

Hom.:

11337

Bravo

AF:

0.839

Asia WGS

AF:

0.959

AC:

3335

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.6

DANN

Benign

0.38

La Branchor

0.77

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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