Variant chr1-1050066-G-T 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.4879+29G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,355,900 control chromosomes in the GnomAD database, including 122,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9412 hom., cov: 28)

Exomes 𝑓: 0.45 ( 112969 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.24

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=-0.89).

BP6

Variant 1-1050066-G-T is Benign according to our data. Variant chr1-1050066-G-T is described in ClinVar as [Benign]. Clinvar id is 263191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 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.4879+29G>T		intron_variant		ENST00000379370.7	NP_940978.2	O00468-6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AGRN	ENST00000379370.7 linkuse as main transcript	c.4879+29G>T	intron_variant	1	NM_198576.4	ENSP00000368678.2	O00468-6
AGRN	ENST00000651234.1 linkuse as main transcript	c.4564+29G>T	intron_variant			ENSP00000499046.1	A0A494C1I6
AGRN	ENST00000652369.1 linkuse as main transcript	c.4564+29G>T	intron_variant			ENSP00000498543.1	A0A494C0G5
AGRN	ENST00000620552.4 linkuse as main transcript	c.4465+29G>T	intron_variant	5		ENSP00000484607.1	A0A087X208

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

49304

AN:

140174

Hom.:

9412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.474

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.380

GnomAD3 exomes

AF:

0.415

AC:

53611

AN:

129156

Hom.:

9753

AF XY:

0.422

AC XY:

29804

AN XY:

70552

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.446

AC:

542767

AN:

1215632

Hom.:

112969

Cov.:

AF XY:

0.445

AC XY:

268308

AN XY:

602956

show subpopulations

Gnomad4 AFR exome

AF:

0.0991

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.437

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.442

Gnomad4 FIN exome

AF:

0.388

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.352

AC:

49310

AN:

140268

Hom.:

9412

Cov.:

AF XY:

0.353

AC XY:

24135

AN XY:

68414

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.450

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.182

Hom.:

293

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 28, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.20

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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