rs12086219

Variant names:

• chr1-48755631-G-A
• rs12086219
• NM_032785.4:c.635-92390C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-48755631-G-A
• chr1-48755631-G-C

Variant summary

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

The NM_032785.4(AGBL4):​c.635-92390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 152,190 control chromosomes in the GnomAD database, including 699 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 0.081 (699 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 2 publications found

Genes affected

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

BEND5 (HGNC:25668): (BEN domain containing 5) Predicted to enable DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Predicted to be located in Golgi apparatus. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032785.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	NM_032785.4	MANE Select	c.635-92390C>T		intron	N/A	NP_116174.3
	BEND5	NM_024603.4	MANE Select	c.745+3269C>T		intron	N/A	NP_078879.2
	AGBL4	NM_001323574.2		c.671-92390C>T		intron	N/A	NP_001310503.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.635-92390C>T		intron	N/A	ENSP00000360905.1
	BEND5	ENST00000371833.4	TSL:1 MANE Select	c.745+3269C>T		intron	N/A	ENSP00000360899.3
	AGBL4	ENST00000416121.5	TSL:1	c.170-92390C>T		intron	N/A	ENSP00000401622.1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12381 AN: 152072 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0665

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

GnomAD4 genome AF: 0.0815 AC: 12403 AN: 152190 Hom.: 699 Cov.: 32 AF XY: 0.0822 AC XY: 6114 AN XY: 74404

African (AFR) AF: 0.135 AC: 5610 AN: 41504

American (AMR) AF: 0.138 AC: 2105 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.170 AC: 878 AN: 5160

South Asian (SAS) AF: 0.0797 AC: 384 AN: 4820

European-Finnish (FIN) AF: 0.0345 AC: 366 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2721 AN: 68006

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0676 Hom.: 149

Bravo AF: 0.0933

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.78
PhyloP100		-0.65
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: rs12086219; hg19: chr1-49221303;