Variant rs2710876 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 NM_198576.4(AGRN):c.1384+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 1,576,312 control chromosomes in the GnomAD database, including 643,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 50654 hom., cov: 34)

Exomes 𝑓: 0.91 ( 593093 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.73

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-1042190-G-A is Benign according to our data. Variant chr1-1042190-G-A is described in ClinVar as [Benign]. Clinvar id is 263159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 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.1384+28G>A		intron_variant		ENST00000379370.7	NP_940978.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
AGRN	ENST00000379370.7 linkuse as main transcript	c.1384+28G>A	intron_variant	1	NM_198576.4	ENSP00000368678	P1	O00468-6
AGRN	ENST00000620552.4 linkuse as main transcript	c.970+28G>A	intron_variant	5		ENSP00000484607
AGRN	ENST00000651234.1 linkuse as main transcript	c.1069+28G>A	intron_variant			ENSP00000499046
AGRN	ENST00000652369.1 linkuse as main transcript	c.1069+28G>A	intron_variant			ENSP00000498543

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119832

AN:

152074

Hom.:

50662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.986

Gnomad AMR

AF:

0.883

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.968

Gnomad SAS

AF:

0.947

Gnomad FIN

AF:

0.940

Gnomad MID

AF:

0.879

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.825

GnomAD3 exomes

AF:

0.897

AC:

193293

AN:

215414

Hom.:

88240

AF XY:

0.905

AC XY:

108077

AN XY:

119420

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.932

Gnomad ASJ exome

AF:

0.918

Gnomad EAS exome

AF:

0.973

Gnomad SAS exome

AF:

0.945

Gnomad FIN exome

AF:

0.937

Gnomad NFE exome

AF:

0.915

Gnomad OTH exome

AF:

0.899

GnomAD4 exome

AF:

0.909

AC:

1294784

AN:

1424120

Hom.:

593093

Cov.:

AF XY:

0.911

AC XY:

642591

AN XY:

704992

show subpopulations

Gnomad4 AFR exome

AF:

0.418

Gnomad4 AMR exome

AF:

0.925

Gnomad4 ASJ exome

AF:

0.915

Gnomad4 EAS exome

AF:

0.970

Gnomad4 SAS exome

AF:

0.943

Gnomad4 FIN exome

AF:

0.932

Gnomad4 NFE exome

AF:

0.919

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

AF:

0.787

AC:

119841

AN:

152192

Hom.:

50654

Cov.:

AF XY:

0.793

AC XY:

59006

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.441

Gnomad4 AMR

AF:

0.883

Gnomad4 ASJ

AF:

0.920

Gnomad4 EAS

AF:

0.968

Gnomad4 SAS

AF:

0.946

Gnomad4 FIN

AF:

0.940

Gnomad4 NFE

AF:

0.918

Gnomad4 OTH

AF:

0.826

Alfa

AF:

0.863

Hom.:

10711

Bravo

AF:

0.766

Asia WGS

AF:

0.921

AC:

3205

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

-0.84

CADD

Benign

0.15

DANN

Benign

0.66

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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