15-86648689-T-G

Variant names:

• chr15-86648689-T-G
• rs2469183
• NM_001386094.1:c.2995-25584T>G

Variant summary

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

The NM_001386094.1(AGBL1):​c.2995-25584T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,874 control chromosomes in the GnomAD database, including 22,213 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 0.54 (22213 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.2995-25584T>G		intron_variant	Intron 21 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.2995-25584T>G		intron_variant	Intron 21 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.3058-25584T>G		intron_variant	Intron 22 of 24	5		ENSP00000413001.3
AGBL1	ENST00000681381.1	n.154-25584T>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81848 AN: 151756 Hom.: 22207 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.539 AC: 81895 AN: 151874 Hom.: 22213 Cov.: 32 AF XY: 0.536 AC XY: 39754 AN XY: 74204

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.560

Alfa AF: 0.544 Hom.: 44226

Bravo AF: 0.546

Asia WGS AF: 0.517 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.27

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: rs2469183; hg19: chr15-87191920;