rs4732082

chr7-135033654-G-Achr7-135033654-G-Cchr7-135033654-G-T

Variant summary

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

The NM_178563.4(AGBL3):c.558-495G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,080 control chromosomes in the GnomAD database, including 15,583 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 0.44 (15583 hom., cov: 32)
• Consequence: AGBL3 NM_178563.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

Genes affected

AGBL3 (HGNC:27981): (AGBL carboxypeptidase 3) Enables metallocarboxypeptidase activity. Involved in protein side chain deglutamylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL3	NM_178563.4	c.558-495G>A		intron_variant		ENST00000436302.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL3	ENST00000436302.6	c.558-495G>A		intron_variant		2	NM_178563.4	P2
AGBL3	ENST00000275763.10	c.558-495G>A		intron_variant, NMD_transcript_variant		1
AGBL3	ENST00000435976.6	c.558-495G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67406 AN: 151962 Hom.: 15584 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.443 AC: 67430 AN: 152080 Hom.: 15583 Cov.: 32 AF XY: 0.445 AC XY: 33096 AN XY: 74340

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.456

Alfa AF: 0.463 Hom.: 2881

Bravo AF: 0.440

Asia WGS AF: 0.495 AC: 1717 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	16
Dann	Benign	0.62

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: rs4732082; hg19: chr7-134718405; COSMIC: COSV51952772;