rs2257019

chr15-86587796-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386094.1(AGBL1):c.2994+33259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,288 control chromosomes in the GnomAD database, including 69,451 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 0.95 (69451 hom., cov: 33)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.2994+33259C>T		intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.2994+33259C>T		intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000441037.7	c.3057+31511C>T		intron_variant		5		A2
AGBL1	ENST00000681381.1	n.153+8960C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145238 AN: 152170 Hom.: 69406 Cov.: 33

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.966

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

GnomAD4 genome AF: 0.954 AC: 145341 AN: 152288 Hom.: 69451 Cov.: 33 AF XY: 0.952 AC XY: 70918 AN XY: 74466

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.966

Alfa AF: 0.966 Hom.: 16016

Bravo AF: 0.952

Asia WGS AF: 0.954 AC: 3316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.61
Dann	Benign	0.55

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: rs2257019; hg19: chr15-87131027;