15-87007639-T-G

Position:

• chr15-87007639-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL1	NM_152336.4	c.3323+19551T>G		intron_variant			NP_689549.3
AGBL1	XM_011521227.4	c.3159-21186T>G		intron_variant			XP_011519529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000441037.7	c.3323+19551T>G		intron_variant		5		ENSP00000413001.3
AGBL1	ENST00000681381.1	n.318-34366T>G		intron_variant

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

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.881

Alfa AF: 0.906 Hom.: 64838

Bravo AF: 0.855

Asia WGS AF: 0.940 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs1433446; hg19: chr15-87550870;