rs1433456

chr15-86935142-G-Achr15-86935142-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_135682.1(LOC105370954):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: LOC105370954 NR_135682.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716

Genes affected

(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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105370954	NR_135682.1	n.150G>A		non_coding_transcript_exon_variant	2/3
AGBL1	NM_152336.4	c.3222-52845G>A		intron_variant
AGBL1	XM_011521227.4	c.3159-93683G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000560696.1	n.150G>A		non_coding_transcript_exon_variant	2/3	3
AGBL1	ENST00000441037.7	c.3222-52845G>A		intron_variant		5		A2
AGBL1	ENST00000681381.1	n.318-106863G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0796

Gnomad4 EAS AF: 0.0573

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0894

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0849 Hom.: 258

Bravo AF: 0.130

Asia WGS AF: 0.169 AC: 587 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	6.2
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1433456; hg19: chr15-87478373;