chr15-86935142-G-A

Variant names:

• chr15-86935142-G-A
• rs1433456
• ENST00000560696.1:n.150G>A

Variant summary

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

The ENST00000560696.1(ENSG00000259636):​n.150G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,936 control chromosomes in the GnomAD database, including 1,775 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 (1775 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: ENSG00000259636 ENST00000560696.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 3 publications found

Genes affected

ENSG00000259636 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000560696.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC105370954	NR_135682.1		n.150G>A		non_coding_transcript_exon	Exon 2 of 3
	AGBL1	NM_152336.4		c.3222-52845G>A		intron	N/A	NP_689549.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000259636	ENST00000560696.1	TSL:3	n.150G>A		non_coding_transcript_exon	Exon 2 of 3
	AGBL1	ENST00000441037.7	TSL:5	c.3222-52845G>A		intron	N/A	ENSP00000413001.3
	AGBL1	ENST00000681381.1		n.318-106863G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18679 AN: 151808 Hom.: 1765 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.123 AC: 18718 AN: 151926 Hom.: 1775 Cov.: 32 AF XY: 0.126 AC XY: 9357 AN XY: 74264

African (AFR) AF: 0.253 AC: 10473 AN: 41358

American (AMR) AF: 0.114 AC: 1746 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3468

East Asian (EAS) AF: 0.0573 AC: 296 AN: 5162

South Asian (SAS) AF: 0.203 AC: 974 AN: 4808

European-Finnish (FIN) AF: 0.0894 AC: 945 AN: 10570

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0547 AC: 3718 AN: 67982

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.0885 Hom.: 353

Bravo AF: 0.130

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.59
PhyloP100		0.72
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: rs1433456; hg19: chr15-87478373;