rs3905053

Positions:

• chr1-49067028-A-G

Variant summary

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

The NM_032785.4(AGBL4):​c.378-21228T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,990 control chromosomes in the GnomAD database, including 31,063 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 0.63 (31063 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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]

ENSG00000229846 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.378-21228T>C		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.378-21228T>C		intron_variant		2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000371836.1	c.378-21228T>C		intron_variant		1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.378-21228T>C		intron_variant		5		ENSP00000360904.1
ENSG00000229846	ENST00000456002.2	n.178+18615A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95953 AN: 151872 Hom.: 31029 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.632 AC: 96033 AN: 151990 Hom.: 31063 Cov.: 32 AF XY: 0.624 AC XY: 46386 AN XY: 74280

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.645

Alfa AF: 0.633 Hom.: 4490

Bravo AF: 0.645

Asia WGS AF: 0.355 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.31

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: rs3905053; hg19: chr1-49532700;