Variant rs183108359 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198576.4(AGRN):c.2536+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00879 in 1,607,566 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 12 hom., cov: 34)

Exomes 𝑓: 0.0090 ( 222 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.506

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:

AGRN (HGNC:):

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=-0.82).

BP6

Variant 1-1045568-C-T is Benign according to our data. Variant chr1-1045568-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 263171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00662 (1006/152026) while in subpopulation SAS AF= 0.0408 (197/4830). AF 95% confidence interval is 0.0361. There are 12 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGRN	NM_198576.4 linkuse as main transcript	c.2536+45C>T		intron_variant		ENST00000379370.7	NP_940978.2	O00468-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGRN	ENST00000379370.7 linkuse as main transcript	c.2536+45C>T		intron_variant		1	NM_198576.4	ENSP00000368678.2		O00468-6

Frequencies

GnomAD3 genomes

AF:

0.00665

AC:

1010

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0414

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00670

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0114

AC:

2760

AN:

242968

Hom.:

AF XY:

0.0133

AC XY:

1758

AN XY:

132320

show subpopulations

Gnomad AFR exome

AF:

0.00201

Gnomad AMR exome

AF:

0.00510

Gnomad ASJ exome

AF:

0.0379

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.0435

Gnomad FIN exome

AF:

0.000651

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.00901

AC:

13118

AN:

1455540

Hom.:

222

Cov.:

AF XY:

0.0103

AC XY:

7475

AN XY:

723322

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.00513

Gnomad4 ASJ exome

AF:

0.0384

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0435

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.00631

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.00662

AC:

1006

AN:

152026

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

546

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00167

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.0397

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00670

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00984

Hom.:

Bravo

AF:

0.00583

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 05, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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

-0.82

CADD

Benign

1.8

DANN

Benign

0.47

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