rs12914656

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
AGBL1NM_001386094.1 linkuse as main transcriptc.52-24515T>C intron_variant ENST00000614907.3 NP_001373023.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGBL1ENST00000614907.3 linkuse as main transcriptc.52-24515T>C intron_variant 5 NM_001386094.1 ENSP00000490608 P4
AGBL1ENST00000441037.7 linkuse as main transcriptc.52-24515T>C intron_variant 5 ENSP00000413001 A2

Frequencies

GnomAD3 genomes
AF:
0.119
AC:
18043
AN:
152050
Hom.:
1165
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.0933
Gnomad4 AMR
AF:
0.0863
Gnomad4 ASJ
AF:
0.126
Gnomad4 EAS
AF:
0.250
Gnomad4 SAS
AF:
0.138
Gnomad4 FIN
AF:
0.198
Gnomad4 NFE
AF:
0.117
Gnomad4 OTH
AF:
0.119
Alfa
AF:
0.109
Hom.:
172
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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12914656; hg19: chr15-86660720; API