rs12914656

Variant names:

• chr15-86117489-T-C
• rs12914656
• NM_001386094.1:c.52-24515T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386094.1(AGBL1):​c.52-24515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,168 control chromosomes in the GnomAD database, including 1,171 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 0.12 (1171 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.52-24515T>C		intron_variant	Intron 1 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.52-24515T>C		intron_variant	Intron 1 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.52-24515T>C		intron_variant	Intron 1 of 24	5		ENSP00000413001.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18043 AN: 152050 Hom.: 1165 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.119 AC: 18065 AN: 152168 Hom.: 1171 Cov.: 32 AF XY: 0.123 AC XY: 9177 AN XY: 74360

African (AFR) AF: 0.0933 AC: 3874 AN: 41534

American (AMR) AF: 0.0863 AC: 1319 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1290 AN: 5170

South Asian (SAS) AF: 0.138 AC: 662 AN: 4814

European-Finnish (FIN) AF: 0.198 AC: 2099 AN: 10576

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7960 AN: 68008

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.113 Hom.: 542

Bravo AF: 0.111

Asia WGS AF: 0.193 AC: 669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.89
PhyloP100		-0.090

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12914656; hg19: chr15-86660720;