rs16977195

Variant names:

• chr15-86441009-A-G
• rs16977195
• NM_001386094.1:c.2555+43463A>G

Variant summary

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

The NM_001386094.1(AGBL1):​c.2555+43463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,266 control chromosomes in the GnomAD database, including 233 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 0.044 (233 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.2555+43463A>G		intron_variant	Intron 18 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.2555+43463A>G		intron_variant	Intron 18 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.2555+43463A>G		intron_variant	Intron 18 of 24	5		ENSP00000413001.3

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6634 AN: 152148 Hom.: 234 Cov.: 32

Gnomad AFR AF: 0.00963

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0899

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0436 AC: 6632 AN: 152266 Hom.: 233 Cov.: 32 AF XY: 0.0450 AC XY: 3352 AN XY: 74464

African (AFR) AF: 0.00960 AC: 399 AN: 41566

American (AMR) AF: 0.0218 AC: 334 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3470

East Asian (EAS) AF: 0.147 AC: 762 AN: 5174

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4822

European-Finnish (FIN) AF: 0.0899 AC: 953 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3661 AN: 68010

Other (OTH) AF: 0.0299 AC: 63 AN: 2110

Alfa AF: 0.0494 Hom.: 699

Bravo AF: 0.0367

Asia WGS AF: 0.0900 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.64
PhyloP100		1.2
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: rs16977195; hg19: chr15-86984240;