rs4887244

Positions:

• chr15-86803618-G-A

Variant summary

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

The NM_001386094.1(AGBL1):​c.3159-103469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,112 control chromosomes in the GnomAD database, including 1,435 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 0.11 (1435 hom., cov: 32)
• Consequence: AGBL1 NM_001386094.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1	c.3159-103469G>A		intron_variant		ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3	c.3159-103469G>A		intron_variant		5	NM_001386094.1	P4
AGBL1	ENST00000441037.7	c.3221+129182G>A		intron_variant		5		A2
AGBL1	ENST00000681381.1	n.317+129182G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16702 AN: 151994 Hom.: 1439 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0993

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

GnomAD4 genome AF: 0.110 AC: 16721 AN: 152112 Hom.: 1435 Cov.: 32 AF XY: 0.111 AC XY: 8257 AN XY: 74344

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0978

Alfa AF: 0.0783 Hom.: 173

Bravo AF: 0.125

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.60

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: rs4887244; hg19: chr15-87346849; COSMIC: COSV66852695;