rs17231212

Variant names:

• chr7-135100989-T-C
• rs17231212
• NM_178563.4:c.2111-14391T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178563.4(AGBL3):​c.2111-14391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 152,324 control chromosomes in the GnomAD database, including 454 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 0.060 (454 hom., cov: 32)
• Consequence: AGBL3 NM_178563.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL3	NM_178563.4	c.2111-14391T>C		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.2111-14391T>C		intron_variant	Intron 15 of 16	2	NM_178563.4	ENSP00000388275.2

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9194 AN: 152206 Hom.: 454 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0603 AC: 9190 AN: 152324 Hom.: 454 Cov.: 32 AF XY: 0.0596 AC XY: 4442 AN XY: 74484

African (AFR) AF: 0.0165 AC: 688 AN: 41584

American (AMR) AF: 0.0485 AC: 742 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3466

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.0132 AC: 64 AN: 4832

European-Finnish (FIN) AF: 0.108 AC: 1145 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0921 AC: 6265 AN: 68004

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0805 Hom.: 2127

Bravo AF: 0.0549

Asia WGS AF: 0.00809 AC: 28 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.86
PhyloP100		-0.90
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: rs17231212; hg19: chr7-134785741;