chr1-49465077-T-C

Position:

• chr1-49465077-T-C

Variant summary

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

The NM_032785.4(AGBL4):​c.283-219213A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,456 control chromosomes in the GnomAD database, including 16,293 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 0.42 (16293 hom., cov: 31)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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]

AGBL4-IT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.283-219213A>G		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.283-219213A>G		intron_variant		2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000371836.1	c.283-219213A>G		intron_variant		1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.283-219213A>G		intron_variant		5		ENSP00000360904.1
AGBL4-IT1	ENST00000457061.1	n.298+4722A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64272 AN: 151338 Hom.: 16295 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.424 AC: 64269 AN: 151456 Hom.: 16293 Cov.: 31 AF XY: 0.419 AC XY: 30998 AN XY: 74004

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.466

Alfa AF: 0.536 Hom.: 21778

Bravo AF: 0.412

Asia WGS AF: 0.206 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.77
DANN	Benign	0.69

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: rs1415985; hg19: chr1-49930749;