chr15-86648689-T-G

Variant names:

• chr15-86648689-T-G
• rs2469183
• NM_001386094.1:c.2995-25584T>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.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
• Publications: 4 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=-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

African (AFR) AF: 0.562 AC: 23270 AN: 41406

American (AMR) AF: 0.539 AC: 8217 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2417 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2629 AN: 5160

South Asian (SAS) AF: 0.486 AC: 2342 AN: 4814

European-Finnish (FIN) AF: 0.455 AC: 4804 AN: 10552

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.535 AC: 36340 AN: 67920

Other (OTH) AF: 0.560 AC: 1181 AN: 2110

Alfa AF: 0.544 Hom.: 69049

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
PhyloP100		-0.20
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: rs2469183; hg19: chr15-87191920;