Variant 1-1049467-G-C 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.4514+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,600,510 control chromosomes in the GnomAD database, including 1,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 732 hom., cov: 32)

Exomes 𝑓: 0.013 ( 713 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.863

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 1-1049467-G-C is Benign according to our data. Variant chr1-1049467-G-C is described in ClinVar as [Benign]. Clinvar id is 263186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 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.4514+16G>C		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.4514+16G>C	intron_variant	1	NM_198576.4	ENSP00000368678	P1	O00468-6
AGRN	ENST00000620552.4 linkuse as main transcript	c.4100+16G>C	intron_variant	5		ENSP00000484607
AGRN	ENST00000651234.1 linkuse as main transcript	c.4199+16G>C	intron_variant			ENSP00000499046
AGRN	ENST00000652369.1 linkuse as main transcript	c.4199+16G>C	intron_variant			ENSP00000498543

Frequencies

GnomAD3 genomes

AF:

0.0592

AC:

8999

AN:

152058

Hom.:

728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00921

Gnomad OTH

AF:

0.0507

GnomAD3 exomes

AF:

0.0203

AC:

4813

AN:

236558

Hom.:

282

AF XY:

0.0162

AC XY:

2102

AN XY:

129432

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.00494

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00277

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.00944

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0125

AC:

18123

AN:

1448334

Hom.:

713

Cov.:

AF XY:

0.0118

AC XY:

8532

AN XY:

721038

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.00529

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00410

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.0203

GnomAD4 genome

AF:

0.0594

AC:

9041

AN:

152176

Hom.:

732

Cov.:

AF XY:

0.0570

AC XY:

4242

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.0280

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00921

Gnomad4 OTH

AF:

0.0502

Alfa

AF:

0.00242

Hom.:

Bravo

AF:

0.0683

Asia WGS

AF:

0.0160

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 20, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital myasthenic syndrome 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.3

DANN

Benign

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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