rs7176964

Variant names:

• chr15-86898503-T-A
• rs7176964
• NM_001386094.1:c.3159-8584T>A

Variant summary

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

The NM_001386094.1(AGBL1):​c.3159-8584T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,088 control chromosomes in the GnomAD database, including 2,743 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 0.16 (2743 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL1	NM_001386094.1	c.3159-8584T>A		intron_variant	Intron 22 of 22	ENST00000614907.3	NP_001373023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL1	ENST00000614907.3	c.3159-8584T>A		intron_variant	Intron 22 of 22	5	NM_001386094.1	ENSP00000490608.2
AGBL1	ENST00000441037.7	c.3222-89484T>A		intron_variant	Intron 23 of 24	5		ENSP00000413001.3
AGBL1	ENST00000681381.1	n.318-143502T>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24492 AN: 151970 Hom.: 2739 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.161 AC: 24520 AN: 152088 Hom.: 2743 Cov.: 32 AF XY: 0.163 AC XY: 12106 AN XY: 74328

African (AFR) AF: 0.318 AC: 13170 AN: 41460

American (AMR) AF: 0.158 AC: 2410 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.119 AC: 615 AN: 5158

South Asian (SAS) AF: 0.0412 AC: 199 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1540 AN: 10584

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0860 AC: 5846 AN: 67984

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.129 Hom.: 210

Bravo AF: 0.170

Asia WGS AF: 0.116 AC: 407 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.53
PhyloP100		0.31
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: rs7176964; hg19: chr15-87441734;