rs1962522

chr7-135101597-C-A

Variant summary

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

The NM_178563.4(AGBL3):c.2111-13783C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,950 control chromosomes in the GnomAD database, including 18,228 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 0.48 (18228 hom., cov: 31)
• Consequence: AGBL3 NM_178563.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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]

CYREN (HGNC:22432): (cell cycle regulator of NHEJ) Involved in double-strand break repair via nonhomologous end joining and negative regulation of double-strand break repair via nonhomologous end joining. Located in cytoplasm and nucleus. [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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL3	NM_178563.4	c.2111-13783C>A		intron_variant		ENST00000436302.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL3	ENST00000436302.6	c.2111-13783C>A		intron_variant		2	NM_178563.4	P2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73603 AN: 151832 Hom.: 18207 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.485 AC: 73678 AN: 151950 Hom.: 18228 Cov.: 31 AF XY: 0.484 AC XY: 35946 AN XY: 74254

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.482

Alfa AF: 0.513 Hom.: 19819

Bravo AF: 0.479

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.65

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: rs1962522; hg19: chr7-134786349;