NM_032785.4:c.951+14462T>A

Variant names:

• chr1-48620031-A-T
• rs320029
• NM_032785.4:c.951+14462T>A

Variant summary

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

The NM_032785.4(AGBL4):​c.951+14462T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,016 control chromosomes in the GnomAD database, including 20,749 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 0.50 (20749 hom., cov: 31)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 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.951+14462T>A		intron	N/A	NP_116174.3
	AGBL4	NM_001323574.2		c.987+14462T>A		intron	N/A	NP_001310503.1
	AGBL4	NM_001323573.2		c.987+14462T>A		intron	N/A	NP_001310502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.951+14462T>A		intron	N/A	ENSP00000360905.1
	AGBL4	ENST00000416121.5	TSL:1	c.486+14462T>A		intron	N/A	ENSP00000401622.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75338 AN: 151898 Hom.: 20743 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.496 AC: 75370 AN: 152016 Hom.: 20749 Cov.: 31 AF XY: 0.496 AC XY: 36879 AN XY: 74278

African (AFR) AF: 0.258 AC: 10689 AN: 41466

American (AMR) AF: 0.525 AC: 8022 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2056 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1506 AN: 5166

South Asian (SAS) AF: 0.580 AC: 2787 AN: 4808

European-Finnish (FIN) AF: 0.663 AC: 7000 AN: 10562

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41344 AN: 67944

Other (OTH) AF: 0.515 AC: 1082 AN: 2102

Alfa AF: 0.537 Hom.: 2916

Bravo AF: 0.476

Asia WGS AF: 0.458 AC: 1593 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.9
DANN	Benign	0.82
PhyloP100		2.0
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: rs320029; hg19: chr1-49085703; COSMIC: COSV61891493;