rs10152811

chr15-86311359-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.2374+15951A>C		intron_variant		ENST00000614907.3
AGBL1-AS1	NR_046012.1	n.490+773T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.2374+15951A>C		intron_variant		5	NM_001386094.1	P4
AGBL1-AS1	ENST00000566878.2	n.485+773T>G		intron_variant, non_coding_transcript_variant		3
AGBL1	ENST00000441037.7	c.2374+15951A>C		intron_variant		5		A2
AGBL1-AS1	ENST00000563472.1	n.444+5371T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0606

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.259

Alfa AF: 0.292 Hom.: 732

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

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: rs10152811; hg19: chr15-86854590;