rs320052

chr1-48709804-G-Achr1-48709804-G-T

Variant summary

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

The NM_032785.4(AGBL4):c.635-46563C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 151,574 control chromosomes in the GnomAD database, including 60,703 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 0.88 (60703 hom., cov: 29)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.635-46563C>T		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.635-46563C>T		intron_variant		2	NM_032785.4	P1
AGBL4	ENST00000416121.5	c.172-46563C>T		intron_variant		1
AGBL4	ENST00000371838.5	c.635-46563C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.877 AC: 132791 AN: 151456 Hom.: 60680 Cov.: 29

Gnomad AFR AF: 0.587

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.877 AC: 132860 AN: 151574 Hom.: 60703 Cov.: 29 AF XY: 0.880 AC XY: 65206 AN XY: 74100

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 0.969

Gnomad4 SAS AF: 0.968

Gnomad4 FIN AF: 0.989

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.915

Alfa AF: 0.926 Hom.: 8145

Bravo AF: 0.861

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.40
Dann	Benign	0.51

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: rs320052; hg19: chr1-49175476;