rs2701423

Positions:

• chr15-86953226-C-T

Variant summary

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

The NM_152336.4(AGBL1):​c.3222-34761C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,176 control chromosomes in the GnomAD database, including 59,531 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 0.88 (59531 hom., cov: 31)
• Consequence: AGBL1 NM_152336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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]

ENSG00000259620 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL1	NM_152336.4	c.3222-34761C>T		intron_variant			NP_689549.3
AGBL1	XM_011521227.4	c.3159-75599C>T		intron_variant			XP_011519529.1
LOC102724452	NR_135683.1	n.91-13460G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000441037.7	c.3222-34761C>T		intron_variant		5		ENSP00000413001.3
ENSG00000259620	ENST00000558587.1	n.91-13460G>A		intron_variant		2
AGBL1	ENST00000681381.1	n.318-88779C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134158 AN: 152058 Hom.: 59473 Cov.: 31

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.882 AC: 134273 AN: 152176 Hom.: 59531 Cov.: 31 AF XY: 0.884 AC XY: 65716 AN XY: 74378

Gnomad4 AFR AF: 0.959

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.968

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.884

Alfa AF: 0.858 Hom.: 9477

Bravo AF: 0.886

Asia WGS AF: 0.937 AC: 3259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15
DANN	Benign	0.18

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: rs2701423; hg19: chr15-87496457;