rs10520618

Positions:

• chr15-86264530-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001386094.1(AGBL1):​c.1359A>G​(p.Glu453=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,613,684 control chromosomes in the GnomAD database, including 149,103 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 0.49 (18798 hom., cov: 32)
  • Exomes 𝑓: 0.42 (130305 hom.)
• Consequence: AGBL1 NM_001386094.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.1359A>G	p.Glu453=	synonymous_variant	11/23	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.1359A>G	p.Glu453=	synonymous_variant	11/23	5	NM_001386094.1	ENSP00000490608	P4
AGBL1	ENST00000568785.5	n.543A>G		non_coding_transcript_exon_variant	2/8	1
AGBL1	ENST00000441037.7	c.1359A>G	p.Glu453=	synonymous_variant	11/25	5		ENSP00000413001	A2
AGBL1	ENST00000567715.1	n.433A>G		non_coding_transcript_exon_variant	3/9	2

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73828 AN: 151988 Hom.: 18772 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.491

GnomAD3 exomes AF: 0.435 AC: 108425 AN: 248984 Hom.: 24377 AF XY: 0.437 AC XY: 59032 AN XY: 135074

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.357

Gnomad SAS exome AF: 0.498

Gnomad FIN exome AF: 0.379

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.418 AC: 611605 AN: 1461578 Hom.: 130305 Cov.: 72 AF XY: 0.421 AC XY: 306079 AN XY: 727056

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.494

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.486 AC: 73901 AN: 152106 Hom.: 18798 Cov.: 32 AF XY: 0.482 AC XY: 35850 AN XY: 74352

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.489

Alfa AF: 0.444 Hom.: 21988

Bravo AF: 0.495

Asia WGS AF: 0.463 AC: 1614 AN: 3478

EpiCase AF: 0.430

EpiControl AF: 0.440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.62

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: rs10520618; hg19: chr15-86807761; COSMIC: COSV66850936;