Variant 1-1051380-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 263198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.5370+11G>A		intron_variant		ENST00000379370.7	NP_940978.2	O00468-6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AGRN	ENST00000379370.7 link	c.5370+11G>A	intron_variant	1	NM_198576.4	ENSP00000368678.2	O00468-6
AGRN	ENST00000651234.1 link	c.5067+11G>A	intron_variant			ENSP00000499046.1	A0A494C1I6
AGRN	ENST00000652369.1 link	c.5055+11G>A	intron_variant			ENSP00000498543.1	A0A494C0G5
AGRN	ENST00000620552.4 link	c.4968+11G>A	intron_variant	5		ENSP00000484607.1	A0A087X208

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

GnomAD3 exomes

AF:

0.000907

AC:

144

AN:

158752

Hom.:

AF XY:

0.000874

AC XY:

AN XY:

85772

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 SAS exome

AF:

0.0000845

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

Gnomad4 AFR exome

AF:

0.0000921

Gnomad4 AMR exome

AF:

0.000406

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000212

Gnomad4 FIN exome

AF:

0.000224

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.000979

AC:

149

AN:

152232

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.000473

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

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 13, 2016	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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.2

DANN

Benign

0.82

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