1-48620031-A-T

Position:

• chr1-48620031-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.951+14462T>A		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.951+14462T>A		intron_variant		2	NM_032785.4	P1
AGBL4	ENST00000416121.5	c.488+14462T>A		intron_variant		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

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.515

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.9
DANN	Benign	0.82

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: rs320029; hg19: chr1-49085703; COSMIC: COSV61891493;