rs12901001

Variant names:

• chr15-86316245-A-G
• rs12901001
• NM_001386094.1:c.2374+20837A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-86316245-A-G
• chr15-86316245-A-T

Variant summary

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

The NM_001386094.1(AGBL1):​c.2374+20837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,064 control chromosomes in the GnomAD database, including 27,742 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 0.60 (27742 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 6 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-AS1 (HGNC:48617): (AGBL1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.2374+20837A>G		intron_variant	Intron 17 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.2374+20837A>G		intron_variant	Intron 17 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.2374+20837A>G		intron_variant	Intron 17 of 24	5		ENSP00000413001.3
AGBL1-AS1	ENST00000563472.2	n.444+485T>C		intron_variant	Intron 1 of 2	3
AGBL1-AS1	ENST00000566878.2	n.234+485T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90720 AN: 151944 Hom.: 27746 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.597 AC: 90743 AN: 152064 Hom.: 27742 Cov.: 32 AF XY: 0.590 AC XY: 43849 AN XY: 74322

African (AFR) AF: 0.504 AC: 20907 AN: 41462

American (AMR) AF: 0.569 AC: 8698 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2279 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1914 AN: 5158

South Asian (SAS) AF: 0.514 AC: 2477 AN: 4820

European-Finnish (FIN) AF: 0.645 AC: 6818 AN: 10572

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45650 AN: 67976

Other (OTH) AF: 0.616 AC: 1298 AN: 2108

Alfa AF: 0.644 Hom.: 101388

Bravo AF: 0.587

Asia WGS AF: 0.466 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.48
PhyloP100		-0.87
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: rs12901001; hg19: chr15-86859476;