rs1962522

Variant names:

• chr7-135101597-C-A
• rs1962522
• NM_178563.4:c.2111-13783C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGBL3	NM_178563.4	c.2111-13783C>A		intron_variant	Intron 15 of 16	ENST00000436302.6	NP_848658.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL3	ENST00000436302.6	c.2111-13783C>A		intron_variant	Intron 15 of 16	2	NM_178563.4	ENSP00000388275.2

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

African (AFR) AF: 0.421 AC: 17455 AN: 41422

American (AMR) AF: 0.505 AC: 7708 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2263 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5168

South Asian (SAS) AF: 0.655 AC: 3154 AN: 4816

European-Finnish (FIN) AF: 0.480 AC: 5055 AN: 10538

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35151 AN: 67944

Other (OTH) AF: 0.482 AC: 1017 AN: 2110

Alfa AF: 0.511 Hom.: 23914

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
PhyloP100		0.033
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: rs1962522; hg19: chr7-134786349;