rs12725018

Positions:

• chr1-49989654-C-A
• chr1-49989654-C-G
• chr1-49989654-C-T

Variant summary

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

The NM_032785.4(AGBL4):​c.34+34109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,984 control chromosomes in the GnomAD database, including 8,398 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 0.32 (8398 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.34+34109G>T		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.34+34109G>T		intron_variant		2	NM_032785.4	ENSP00000360905	P1
AGBL4	ENST00000371836.1	c.34+34109G>T		intron_variant		1		ENSP00000360902
AGBL4	ENST00000371838.5	c.34+34109G>T		intron_variant		5		ENSP00000360904

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48109 AN: 151866 Hom.: 8392 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.317 AC: 48136 AN: 151984 Hom.: 8398 Cov.: 32 AF XY: 0.323 AC XY: 24025 AN XY: 74266

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.308

Alfa AF: 0.316 Hom.: 991

Bravo AF: 0.307

Asia WGS AF: 0.556 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.65

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: rs12725018; hg19: chr1-50455326;