15-86247883-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001386094.1(AGBL1):c.735+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,613,766 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (1 hom.)
• Consequence: AGBL1 NM_001386094.1 splice_donor_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-86247883-G-A is Benign according to our data. Variant chr15-86247883-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.735+4G>A		splice_donor_region_variant, intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.735+4G>A		splice_donor_region_variant, intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000441037.7	c.735+4G>A		splice_donor_region_variant, intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000671 AC: 165 AN: 245976 Hom.: 0 AF XY: 0.000777 AC XY: 104 AN XY: 133878

Gnomad AFR exome AF: 0.000131

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.00420

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000780

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000505 AC: 738 AN: 1461406 Hom.: 1 Cov.: 32 AF XY: 0.000532 AC XY: 387 AN XY: 727002

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.00413

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0000753

Gnomad4 NFE exome AF: 0.000409

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.000466 AC: 71 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74500

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000755 Hom.: 0

Bravo AF: 0.000514

EpiCase AF: 0.000654

EpiControl AF: 0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

AGBL1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.33
Dann	Benign	0.66

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: rs184824180; hg19: chr15-86791114;