Variant 15-86224904-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001386094.1(AGBL1):c.489-10C>T 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 0.0142 in 1,613,060 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 31)

Exomes 𝑓: 0.015 ( 203 hom. )

Consequence

AGBL1
NM_001386094.1 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003197

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.436

Variant links:

Genes affected

AGBL1 (HGNC:26504): (AGBL carboxypeptidase 1) Polyglutamylation is a reversible posttranslational modification catalyzed by polyglutamylases that results in the addition of glutamate side chains on the modified protein. This gene encodes a glutamate decarboxylase that catalyzes the deglutamylation of polyglutamylated proteins. Mutations in this gene result in dominant late-onset Fuchs corneal dystrophy. [provided by RefSeq, Nov 2013]

AGBL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 15-86224904-C-T is Benign according to our data. Variant chr15-86224904-C-T is described in ClinVar as [Benign]. Clinvar id is 3038387.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0104 (1588/152184) while in subpopulation SAS AF= 0.027 (130/4814). AF 95% confidence interval is 0.0232. There are 12 homozygotes in gnomad4. There are 780 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd at 1588 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1 linkuse as main transcript	c.489-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3 linkuse as main transcript	c.489-10C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000441037.7 linkuse as main transcript	c.489-10C>T		splice_polypyrimidine_tract_variant, intron_variant		5		A2

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1588

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0270

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.0135

AC:

3367

AN:

248926

Hom.:

AF XY:

0.0149

AC XY:

2013

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.00824

Gnomad ASJ exome

AF:

0.00856

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0146

AC:

21381

AN:

1460876

Hom.:

203

Cov.:

AF XY:

0.0150

AC XY:

10932

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.00846

Gnomad4 ASJ exome

AF:

0.00774

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0233

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.0104

AC:

1588

AN:

152184

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

780

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0270

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.00966

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AGBL1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00032

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.030

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