Variant rs535286672 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 ENST00000379370.7(AGRN):c.4879+17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 859,976 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

AGRN
ENST00000379370.7 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.260

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=-0.86).

BP6

Variant 1-1050054-T-A is Benign according to our data. Variant chr1-1050054-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 263190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00161 (206/127868) while in subpopulation AFR AF= 0.00642 (191/29768). AF 95% confidence interval is 0.00567. There are 2 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGRN	NM_198576.4 linkuse as main transcript	c.4879+17T>A		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.4879+17T>A	intron_variant	1	NM_198576.4	ENSP00000368678	P1	O00468-6
AGRN	ENST00000620552.4 linkuse as main transcript	c.4465+17T>A	intron_variant	5		ENSP00000484607
AGRN	ENST00000651234.1 linkuse as main transcript	c.4564+17T>A	intron_variant			ENSP00000499046
AGRN	ENST00000652369.1 linkuse as main transcript	c.4564+17T>A	intron_variant			ENSP00000498543

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

205

AN:

127820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00639

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000971

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000160

Gnomad OTH

AF:

0.000561

GnomAD3 exomes

AF:

0.000365

AC:

AN:

137146

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

74844

show subpopulations

Gnomad AFR exome

AF:

0.00653

Gnomad AMR exome

AF:

0.000424

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000459

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000281

AC:

206

AN:

732108

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

AN XY:

376688

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.000478

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000297

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00161

AC:

206

AN:

127868

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

AN XY:

61920

show subpopulations

Gnomad4 AFR

AF:

0.00642

Gnomad4 AMR

AF:

0.000969

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000160

Gnomad4 OTH

AF:

0.000555

Alfa

AF:

0.000940

Hom.:

Bravo

AF:

0.00159

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital myasthenic syndrome 8

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.30

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