1-1055000-C-T

Variant names:

Variant summary

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

The NM_198576.4(AGRN):c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,546,620 control chromosomes in the GnomAD database, including 71,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10257 hom., cov: 35)

Exomes 𝑓: 0.29 ( 60763 hom. )

Consequence

AGRN
NM_198576.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.413

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:

ENSG00000242590 (HGNC:):

ENSG00000242590 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=-0.93).

BP6

Variant 1-1055000-C-T is Benign according to our data. Variant chr1-1055000-C-T is described in ClinVar as [Benign]. Clinvar id is 263157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-1055000-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.*19C>T		3_prime_UTR_variant	Exon 36 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.*19C>T		3_prime_UTR_variant	Exon 36 of 36	1	NM_198576.4	ENSP00000368678.2		O00468-6

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53401

AN:

152020

Hom.:

10237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.347

GnomAD3 exomes

AF:

0.291

AC:

43425

AN:

149096

Hom.:

6740

AF XY:

0.292

AC XY:

23345

AN XY:

79964

show subpopulations

Gnomad AFR exome

AF:

0.523

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.291

AC:

406267

AN:

1394482

Hom.:

60763

Cov.:

AF XY:

0.292

AC XY:

200824

AN XY:

687958

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.311

Gnomad4 FIN exome

AF:

0.347

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.351

AC:

53463

AN:

152138

Hom.:

10257

Cov.:

AF XY:

0.351

AC XY:

26083

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.508

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.318

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.304

Hom.:

2285

Bravo

AF:

0.349

Asia WGS

AF:

0.262

AC:

910

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

Feb 01, 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

Apr 11, 2023

Genome-Nilou Lab

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

-0.93

CADD

Benign

1.1

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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