rs114389542

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_198576.4(AGRN):c.2254+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00735 in 1,597,636 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 85 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 127 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.288

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

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-1044455-G-A is Benign according to our data. Variant chr1-1044455-G-A is described in ClinVar as [Benign]. Clinvar id is 263168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.2254+16G>A		intron_variant	Intron 12 of 35	ENST00000379370.7	NP_940978.2	O00468-6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGRN	ENST00000379370.7 link	c.2254+16G>A	intron_variant	Intron 12 of 35	1	NM_198576.4	ENSP00000368678.2	O00468-6
AGRN	ENST00000651234.1 link	c.1939+16G>A	intron_variant	Intron 11 of 37			ENSP00000499046.1	A0A494C1I6
AGRN	ENST00000652369.1 link	c.1939+16G>A	intron_variant	Intron 11 of 34			ENSP00000498543.1	A0A494C0G5
AGRN	ENST00000620552.4 link	c.1840+16G>A	intron_variant	Intron 12 of 38	5		ENSP00000484607.1	A0A087X208

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3391

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.0317

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0114

AC:

2459

AN:

216482

Hom.:

AF XY:

0.0106

AC XY:

1247

AN XY:

117884

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.00612

Gnomad EAS exome

AF:

0.0271

Gnomad SAS exome

AF:

0.00843

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00948

GnomAD4 exome

AF:

0.00577

AC:

8335

AN:

1445298

Hom.:

127

Cov.:

AF XY:

0.00566

AC XY:

4065

AN XY:

717890

show subpopulations

Gnomad4 AFR exome

AF:

0.0651

Gnomad4 AMR exome

AF:

0.00646

Gnomad4 ASJ exome

AF:

0.00557

Gnomad4 EAS exome

AF:

0.0295

Gnomad4 SAS exome

AF:

0.00913

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.00208

Gnomad4 OTH exome

AF:

0.00951

GnomAD4 genome

AF:

0.0223

AC:

3403

AN:

152338

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1720

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0628

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.0316

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.00245

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.0227

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 31, 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. -

PreventionGenetics, part of Exact Sciences

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

- -

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

-0.90

CADD

Benign

1.7

DANN

Benign

0.44

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