rs10520615

Variant names:

• chr15-86226035-A-G
• rs10520615
• NM_001386094.1:c.526+1084A>G

Variant summary

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

The NM_001386094.1(AGBL1):​c.526+1084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,952 control chromosomes in the GnomAD database, including 6,907 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 0.28 (6907 hom., cov: 31)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.526+1084A>G		intron_variant	Intron 6 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.526+1084A>G		intron_variant	Intron 6 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.526+1084A>G		intron_variant	Intron 6 of 24	5		ENSP00000413001.3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42389 AN: 151834 Hom.: 6902 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.279 AC: 42402 AN: 151952 Hom.: 6907 Cov.: 31 AF XY: 0.279 AC XY: 20751 AN XY: 74268

African (AFR) AF: 0.120 AC: 4963 AN: 41468

American (AMR) AF: 0.386 AC: 5888 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3470

East Asian (EAS) AF: 0.189 AC: 974 AN: 5142

South Asian (SAS) AF: 0.321 AC: 1547 AN: 4814

European-Finnish (FIN) AF: 0.311 AC: 3282 AN: 10554

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23474 AN: 67938

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.301 Hom.: 3970

Bravo AF: 0.276

Asia WGS AF: 0.244 AC: 852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.83
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs10520615; hg19: chr15-86769266;