chr1-1020217-G-T

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.45G>T(p.Pro15Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,393,132 control chromosomes in the GnomAD database, including 77,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7500 hom., cov: 32)

Exomes 𝑓: 0.33 ( 69954 hom. )

Consequence

AGRN
NM_198576.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.853

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=-0.57).

BP6

Variant 1-1020217-G-T is Benign according to our data. Variant chr1-1020217-G-T is described in ClinVar as [Benign]. Clinvar id is 128310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-1020217-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.853 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.45G>T	p.Pro15Pro	synonymous_variant	Exon 1 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.45G>T	p.Pro15Pro	synonymous_variant	Exon 1 of 36	1	NM_198576.4	ENSP00000368678.2		O00468-6
AGRN	ENST00000620552 link	c.-370G>T		5_prime_UTR_variant	Exon 1 of 39	5		ENSP00000484607.1		A0A087X208

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46469

AN:

151260

Hom.:

7503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.343

AC:

17342

AN:

50582

Hom.:

3026

AF XY:

0.344

AC XY:

10482

AN XY:

30440

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.448

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.333

AC:

413987

AN:

1241764

Hom.:

69954

Cov.:

AF XY:

0.334

AC XY:

203698

AN XY:

610058

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.420

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.307

AC:

46464

AN:

151368

Hom.:

7500

Cov.:

AF XY:

0.309

AC XY:

22903

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.319

Hom.:

971

Bravo

AF:

0.289

Asia WGS

AF:

0.241

AC:

819

AN:

3400

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 29, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 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

- -

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

-0.57

CADD

Benign

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

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