1-49025705-G-C

Variant names:

• chr1-49025705-G-C
• rs1361544
• NM_032785.4:c.594+19879C>G

Variant summary

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

The NM_032785.4(AGBL4):​c.594+19879C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,100 control chromosomes in the GnomAD database, including 55,106 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 0.85 (55106 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.594+19879C>G		intron_variant	Intron 5 of 13	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.594+19879C>G		intron_variant	Intron 5 of 13	2	NM_032785.4	ENSP00000360905.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129074 AN: 151982 Hom.: 55076 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.870

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.849 AC: 129156 AN: 152100 Hom.: 55106 Cov.: 32 AF XY: 0.844 AC XY: 62782 AN XY: 74366

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.894

Gnomad4 OTH AF: 0.869

Alfa AF: 0.871 Hom.: 7180

Bravo AF: 0.850

Asia WGS AF: 0.738 AC: 2566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.66

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: rs1361544; hg19: chr1-49491377;