chr15-87007639-T-G

Variant names:

• chr15-87007639-T-G
• rs1433446
• NM_152336.4:c.3323+19551T>G

Variant summary

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

The NM_152336.4(AGBL1):​c.3323+19551T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,160 control chromosomes in the GnomAD database, including 57,356 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 0.86 (57356 hom., cov: 32)
• Consequence: AGBL1 NM_152336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152336.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL1	NM_152336.4		c.3323+19551T>G		intron	N/A	NP_689549.3	Q96MI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL1	ENST00000441037.7	TSL:5	c.3323+19551T>G		intron	N/A	ENSP00000413001.3	Q96MI9
	AGBL1	ENST00000681381.1		n.318-34366T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131511 AN: 152042 Hom.: 57322 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.865 AC: 131598 AN: 152160 Hom.: 57356 Cov.: 32 AF XY: 0.867 AC XY: 64507 AN XY: 74384

African (AFR) AF: 0.755 AC: 31332 AN: 41484

American (AMR) AF: 0.833 AC: 12732 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3013 AN: 3468

East Asian (EAS) AF: 0.930 AC: 4799 AN: 5158

South Asian (SAS) AF: 0.982 AC: 4737 AN: 4826

European-Finnish (FIN) AF: 0.895 AC: 9488 AN: 10602

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62522 AN: 68018

Other (OTH) AF: 0.881 AC: 1862 AN: 2114

Alfa AF: 0.890 Hom.: 88861

Bravo AF: 0.855

Asia WGS AF: 0.940 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.81
PhyloP100		-0.35
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: rs1433446; hg19: chr15-87550870;