rs12127450

Positions:

• chr1-48601342-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.952-10357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,250 control chromosomes in the GnomAD database, including 1,488 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 0.13 (1488 hom., cov: 33)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.952-10357A>G		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.952-10357A>G		intron_variant		2	NM_032785.4	P1
AGBL4	ENST00000416121.5	c.489-10357A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20089 AN: 152130 Hom.: 1491 Cov.: 33

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.132 AC: 20087 AN: 152250 Hom.: 1488 Cov.: 33 AF XY: 0.130 AC XY: 9646 AN XY: 74430

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.132

Alfa AF: 0.166 Hom.: 2997

Bravo AF: 0.126

Asia WGS AF: 0.0720 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.25
DANN	Benign	0.70

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: rs12127450; hg19: chr1-49067014; COSMIC: COSV61891487;