rs12901001

Positions:

• chr15-86316245-A-G
• chr15-86316245-A-T

Variant summary

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

The NM_001386094.1(AGBL1):​c.2374+20837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,064 control chromosomes in the GnomAD database, including 27,742 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 0.60 (27742 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.2374+20837A>G		intron_variant		ENST00000614907.3
AGBL1-AS1	NR_046012.1	n.239+485T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.2374+20837A>G		intron_variant		5	NM_001386094.1	P4
AGBL1-AS1	ENST00000566878.2	n.234+485T>C		intron_variant, non_coding_transcript_variant		3
AGBL1	ENST00000441037.7	c.2374+20837A>G		intron_variant		5		A2
AGBL1-AS1	ENST00000563472.1	n.444+485T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90720 AN: 151944 Hom.: 27746 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.597 AC: 90743 AN: 152064 Hom.: 27742 Cov.: 32 AF XY: 0.590 AC XY: 43849 AN XY: 74322

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.616

Alfa AF: 0.653 Hom.: 65721

Bravo AF: 0.587

Asia WGS AF: 0.466 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.48

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: rs12901001; hg19: chr15-86859476;