rs12591257

Positions:

• chr15-86520858-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.2556-1952A>C		intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.2556-1952A>C		intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000441037.7	c.2556-1952A>C		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.00741

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.0720

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0426

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0365 Hom.: 28

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12591257; hg19: chr15-87064089;