15-86510615-G-T

Variant names:

• chr15-86510615-G-T
• rs2011905
• NM_001386094.1:c.2556-12195G>T

Variant summary

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

The NM_001386094.1(AGBL1):​c.2556-12195G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,798 control chromosomes in the GnomAD database, including 15,568 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 0.44 (15568 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.2556-12195G>T		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.2556-12195G>T		intron_variant	Intron 18 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.2556-12195G>T		intron_variant	Intron 18 of 24	5		ENSP00000413001.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66279 AN: 151678 Hom.: 15555 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.437 AC: 66322 AN: 151798 Hom.: 15568 Cov.: 32 AF XY: 0.445 AC XY: 33018 AN XY: 74188

African (AFR) AF: 0.283 AC: 11730 AN: 41410

American (AMR) AF: 0.420 AC: 6391 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1067 AN: 3466

East Asian (EAS) AF: 0.685 AC: 3524 AN: 5148

South Asian (SAS) AF: 0.531 AC: 2560 AN: 4824

European-Finnish (FIN) AF: 0.623 AC: 6581 AN: 10568

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33060 AN: 67840

Other (OTH) AF: 0.415 AC: 875 AN: 2110

Alfa AF: 0.459 Hom.: 27389

Bravo AF: 0.417

Asia WGS AF: 0.603 AC: 2095 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.5
DANN	Benign	0.43
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2011905; hg19: chr15-87053846;