rs12591257

Variant names:

• chr15-86520858-A-C
• rs12591257
• NM_001386094.1:c.2556-1952A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386094.1(AGBL1):​c.2556-1952A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,300 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.030 (100 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• corneal dystrophy, Fuchs endothelial, 8

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.2556-1952A>C		intron_variant	Intron 18 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.2556-1952A>C		intron_variant	Intron 18 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.2556-1952A>C		intron_variant	Intron 18 of 24	5		ENSP00000413001.3

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4553 AN: 152182 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00743

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0299 AC: 4548 AN: 152300 Hom.: 100 Cov.: 32 AF XY: 0.0292 AC XY: 2178 AN XY: 74462

African (AFR) AF: 0.00741 AC: 308 AN: 41582

American (AMR) AF: 0.0210 AC: 321 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3468

East Asian (EAS) AF: 0.0720 AC: 372 AN: 5164

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4826

European-Finnish (FIN) AF: 0.0336 AC: 357 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0426 AC: 2898 AN: 68026

Other (OTH) AF: 0.0218 AC: 46 AN: 2108

Alfa AF: 0.0372 Hom.: 198

Bravo AF: 0.0286

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.65
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs12591257; hg19: chr15-87064089;