Variant rs35881187 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_198576.4(AGRN):c.1385-15_1385-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,587,886 control chromosomes in the GnomAD database, including 243,783 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 18390 hom., cov: 0)

Exomes 𝑓: 0.55 ( 225393 hom. )

Consequence

AGRN
NM_198576.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.112

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 -16 ACMG points.

BP6

Variant 1-1043223-CCT-C is Benign according to our data. Variant chr1-1043223-CCT-C is described in ClinVar as [Benign]. Clinvar id is 263160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 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.1385-15_1385-14del		splice_polypyrimidine_tract_variant, 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.1385-15_1385-14del	splice_polypyrimidine_tract_variant, intron_variant	1	NM_198576.4	ENSP00000368678	P1	O00468-6
AGRN	ENST00000620552.4 linkuse as main transcript	c.971-15_971-14del	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000484607
AGRN	ENST00000651234.1 linkuse as main transcript	c.1070-15_1070-14del	splice_polypyrimidine_tract_variant, intron_variant			ENSP00000499046
AGRN	ENST00000652369.1 linkuse as main transcript	c.1070-15_1070-14del	splice_polypyrimidine_tract_variant, intron_variant			ENSP00000498543

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67234

AN:

151712

Hom.:

18381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.622

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.477

GnomAD3 exomes

AF:

0.551

AC:

113916

AN:

206582

Hom.:

33576

AF XY:

0.552

AC XY:

61257

AN XY:

110960

show subpopulations

Gnomad AFR exome

AF:

0.0943

Gnomad AMR exome

AF:

0.697

Gnomad ASJ exome

AF:

0.546

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.539

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.553

AC:

794283

AN:

1436056

Hom.:

225393

AF XY:

0.553

AC XY:

393599

AN XY:

711874

show subpopulations

Gnomad4 AFR exome

AF:

0.0899

Gnomad4 AMR exome

AF:

0.684

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.802

Gnomad4 SAS exome

AF:

0.549

Gnomad4 FIN exome

AF:

0.539

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.533

GnomAD4 genome

AF:

0.443

AC:

67250

AN:

151830

Hom.:

18390

Cov.:

AF XY:

0.449

AC XY:

33341

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.557

Gnomad4 EAS

AF:

0.786

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.537

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.504

Hom.:

3738

Bravo

AF:

0.436

Asia WGS

AF:

0.647

AC:

2252

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 8

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 27, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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