Variant rs60074964 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_198576.4(AGRN):c.1603+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,596,854 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 4 hom. )

Consequence

AGRN
NM_198576.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.40

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 1-1043467-G-A is Benign according to our data. Variant chr1-1043467-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 541192.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 = 0.00527 (803/152272) while in subpopulation AFR AF= 0.0183 (759/41550). AF 95% confidence interval is 0.0172. There are 7 homozygotes in gnomad4. There are 363 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGRN	NM_198576.4 linkuse as main transcript	c.1603+10G>A		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.1603+10G>A	intron_variant	1	NM_198576.4	ENSP00000368678.2	O00468-6
AGRN	ENST00000651234.1 linkuse as main transcript	c.1288+10G>A	intron_variant			ENSP00000499046.1	A0A494C1I6
AGRN	ENST00000652369.1 linkuse as main transcript	c.1288+10G>A	intron_variant			ENSP00000498543.1	A0A494C0G5
AGRN	ENST00000620552.4 linkuse as main transcript	c.1189+10G>A	intron_variant	5		ENSP00000484607.1	A0A087X208

Frequencies

GnomAD3 genomes

AF:

0.00526

AC:

800

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

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:

0.0000882

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00136

AC:

303

AN:

222730

Hom.:

AF XY:

0.00103

AC XY:

126

AN XY:

122612

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.000821

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000579

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000401

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.000553

AC:

799

AN:

1444582

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

336

AN XY:

718578

show subpopulations

Gnomad4 AFR exome

AF:

0.0194

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000817

Gnomad4 FIN exome

AF:

0.0000226

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.00527

AC:

803

AN:

152272

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

363

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0183

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00579

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 28, 2019

- -

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

-0.49

CADD

Uncertain

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.71

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.71

Position offset: 1

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