rs2469184

Positions:

• chr15-86648746-A-G
• chr15-86648746-A-T

Variant summary

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

The NM_001386094.1(AGBL1):​c.2995-25527A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,894 control chromosomes in the GnomAD database, including 22,207 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 0.54 (22207 hom., cov: 31)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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=-1.09).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.2995-25527A>G		intron_variant		ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.2995-25527A>G		intron_variant		5	NM_001386094.1	ENSP00000490608	P4
AGBL1	ENST00000441037.7	c.3058-25527A>G		intron_variant		5		ENSP00000413001	A2
AGBL1	ENST00000681381.1	n.154-25527A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81835 AN: 151776 Hom.: 22201 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.539 AC: 81882 AN: 151894 Hom.: 22207 Cov.: 31 AF XY: 0.535 AC XY: 39742 AN XY: 74216

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.562

Alfa AF: 0.543 Hom.: 9046

Bravo AF: 0.547

Asia WGS AF: 0.516 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.21
DANN	Benign	0.28

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: rs2469184; hg19: chr15-87191977;