chr15-86241353-G-A

Variant names:

• chr15-86241353-G-A
• rs4887420
• NM_001386094.1:c.527-6318G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386094.1(AGBL1):​c.527-6318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,192 control chromosomes in the GnomAD database, including 912 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 0.085 (912 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386094.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL1	NM_001386094.1	MANE Select	c.527-6318G>A		intron	N/A	NP_001373023.1
	AGBL1	NM_152336.4		c.527-6318G>A		intron	N/A	NP_689549.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL1	ENST00000614907.3	TSL:5 MANE Select	c.527-6318G>A		intron	N/A	ENSP00000490608.2
	AGBL1	ENST00000441037.7	TSL:5	c.527-6318G>A		intron	N/A	ENSP00000413001.3

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12952 AN: 152074 Hom.: 908 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0524

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0768

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

GnomAD4 genome AF: 0.0853 AC: 12978 AN: 152192 Hom.: 912 Cov.: 32 AF XY: 0.0847 AC XY: 6303 AN XY: 74410

African (AFR) AF: 0.185 AC: 7667 AN: 41500

American (AMR) AF: 0.118 AC: 1801 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.0521 AC: 270 AN: 5182

South Asian (SAS) AF: 0.0280 AC: 135 AN: 4828

European-Finnish (FIN) AF: 0.0472 AC: 501 AN: 10606

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0347 AC: 2358 AN: 68004

Other (OTH) AF: 0.0769 AC: 162 AN: 2106

Alfa AF: 0.0704 Hom.: 268

Bravo AF: 0.0984

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.10
DANN	Benign	0.20
PhyloP100		-0.94
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: rs4887420; hg19: chr15-86784584;