rs8025054

chr15-86272265-A-Gchr15-86272265-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386094.1(AGBL1):c.2075+559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,138 control chromosomes in the GnomAD database, including 41,432 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 0.73 (41432 hom., cov: 33)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.2075+559A>G		intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.2075+559A>G		intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000568785.5	n.1259+559A>G		intron_variant, non_coding_transcript_variant		1
AGBL1	ENST00000441037.7	c.2075+559A>G		intron_variant		5		A2
AGBL1	ENST00000567715.1	n.1149+559A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110925 AN: 152020 Hom.: 41395 Cov.: 33

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.730 AC: 111016 AN: 152138 Hom.: 41432 Cov.: 33 AF XY: 0.726 AC XY: 53982 AN XY: 74378

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.731

Alfa AF: 0.694 Hom.: 15321

Bravo AF: 0.734

Asia WGS AF: 0.620 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.5
Dann	Benign	0.64

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: rs8025054; hg19: chr15-86815496;