rs2701423

Variant names:

• chr15-86953226-C-T
• rs2701423
• NM_152336.4:c.3222-34761C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• corneal dystrophy, Fuchs endothelial, 8

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000259620 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGBL1	NM_152336.4	c.3222-34761C>T		intron_variant	Intron 23 of 24		NP_689549.3
LOC102724452	NR_135683.1	n.91-13460G>A		intron_variant	Intron 1 of 2
AGBL1	XM_011521227.4	c.3159-75599C>T		intron_variant	Intron 22 of 22		XP_011519529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000441037.7	c.3222-34761C>T		intron_variant	Intron 23 of 24	5		ENSP00000413001.3
ENSG00000259620	ENST00000558587.1	n.91-13460G>A		intron_variant	Intron 1 of 2	2
AGBL1	ENST00000681381.1	n.318-88779C>T		intron_variant	Intron 2 of 3

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

African (AFR) AF: 0.959 AC: 39840 AN: 41528

American (AMR) AF: 0.833 AC: 12721 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2987 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4759 AN: 5176

South Asian (SAS) AF: 0.968 AC: 4677 AN: 4830

European-Finnish (FIN) AF: 0.829 AC: 8755 AN: 10564

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57555 AN: 68014

Other (OTH) AF: 0.884 AC: 1871 AN: 2116

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
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2701423; hg19: chr15-87496457;