rs10520615

chr15-86226035-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• 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/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.526+1084A>G		intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.526+1084A>G		intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000441037.7	c.526+1084A>G		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.317

Alfa AF: 0.300 Hom.: 3529

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

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: rs10520615; hg19: chr15-86769266;