chr15-86311359-A-C

Variant names:

• chr15-86311359-A-C
• rs10152811
• NM_001386094.1:c.2374+15951A>C

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+15951A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,140 control chromosomes in the GnomAD database, including 6,167 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 0.28 (6167 hom., cov: 33)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 4 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.2374+15951A>C		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+15951A>C		intron_variant	Intron 17 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.2374+15951A>C		intron_variant	Intron 17 of 24	5		ENSP00000413001.3
AGBL1-AS1	ENST00000563472.2	n.444+5371T>G		intron_variant	Intron 1 of 2	3
AGBL1-AS1	ENST00000566878.2	n.485+773T>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42101 AN: 152022 Hom.: 6166 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.277 AC: 42125 AN: 152140 Hom.: 6167 Cov.: 33 AF XY: 0.274 AC XY: 20389 AN XY: 74386

African (AFR) AF: 0.324 AC: 13459 AN: 41494

American (AMR) AF: 0.254 AC: 3884 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3468

East Asian (EAS) AF: 0.0606 AC: 314 AN: 5182

South Asian (SAS) AF: 0.218 AC: 1053 AN: 4820

European-Finnish (FIN) AF: 0.297 AC: 3137 AN: 10576

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18690 AN: 67998

Other (OTH) AF: 0.259 AC: 547 AN: 2110

Alfa AF: 0.298 Hom.: 2378

Bravo AF: 0.278

Asia WGS AF: 0.183 AC: 641 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.3
DANN	Benign	0.92
PhyloP100		0.59
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: rs10152811; hg19: chr15-86854590;