rs1110287

Positions:

• chr15-86518942-C-A
• chr15-86518942-C-G
• chr15-86518942-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386094.1(AGBL1):​c.2556-3868C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 150,598 control chromosomes in the GnomAD database, including 35,876 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 0.67 (35876 hom., cov: 27)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.2556-3868C>A		intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.2556-3868C>A		intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000441037.7	c.2556-3868C>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 101229 AN: 150478 Hom.: 35818 Cov.: 27

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.673 AC: 101347 AN: 150598 Hom.: 35876 Cov.: 27 AF XY: 0.674 AC XY: 49514 AN XY: 73410

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.596

Alfa AF: 0.577 Hom.: 2329

Bravo AF: 0.674

Asia WGS AF: 0.725 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.40
DANN	Benign	0.36

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: rs1110287; hg19: chr15-87062173;