rs4887244

Variant names:

• chr15-86803618-G-A
• rs4887244
• NM_001386094.1:c.3159-103469G>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.3159-103469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,112 control chromosomes in the GnomAD database, including 1,435 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 0.11 (1435 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 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.3159-103469G>A		intron	N/A	NP_001373023.1
	AGBL1	NM_152336.4		c.3221+129182G>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.3159-103469G>A		intron	N/A	ENSP00000490608.2
	AGBL1	ENST00000441037.7	TSL:5	c.3221+129182G>A		intron	N/A	ENSP00000413001.3
	AGBL1	ENST00000681381.1		n.317+129182G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16702 AN: 151994 Hom.: 1439 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0993

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

GnomAD4 genome AF: 0.110 AC: 16721 AN: 152112 Hom.: 1435 Cov.: 32 AF XY: 0.111 AC XY: 8257 AN XY: 74344

African (AFR) AF: 0.214 AC: 8868 AN: 41486

American (AMR) AF: 0.193 AC: 2939 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3470

East Asian (EAS) AF: 0.103 AC: 531 AN: 5158

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4816

European-Finnish (FIN) AF: 0.0737 AC: 780 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0425 AC: 2890 AN: 68014

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

Alfa AF: 0.0783 Hom.: 173

Bravo AF: 0.125

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		0.0
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: rs4887244; hg19: chr15-87346849; COSMIC: COSV66852695;