NM_001386094.1:c.3159-13573G>A

Variant names:

• chr15-86893514-G-A
• rs17647114
• NM_001386094.1:c.3159-13573G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001386094.1(AGBL1):​c.3159-13573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 152,170 control chromosomes in the GnomAD database, including 184 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 0.033 (184 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.3159-13573G>A		intron_variant	Intron 22 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.3159-13573G>A		intron_variant	Intron 22 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.3222-94473G>A		intron_variant	Intron 23 of 24	5		ENSP00000413001.3
AGBL1	ENST00000681381.1	n.318-148491G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4988 AN: 152052 Hom.: 184 Cov.: 32

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00887

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00882

Gnomad OTH AF: 0.0259

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

GnomAD4 genome AF: 0.0329 AC: 5000 AN: 152170 Hom.: 184 Cov.: 32 AF XY: 0.0319 AC XY: 2376 AN XY: 74410

African (AFR) AF: 0.0911 AC: 3782 AN: 41496

American (AMR) AF: 0.0219 AC: 334 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4812

European-Finnish (FIN) AF: 0.00887 AC: 94 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00882 AC: 600 AN: 68014

Other (OTH) AF: 0.0256 AC: 54 AN: 2108

Alfa AF: 0.0136 Hom.: 44

Bravo AF: 0.0364

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.70
PhyloP100		3.1
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: rs17647114; hg19: chr15-87436745; COSMIC: COSV108230371;