1-48574712-T-C

Position:

• chr1-48574712-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032785.4(AGBL4):​c.1267+12292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,596 control chromosomes in the GnomAD database, including 29,297 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 0.62 (29297 hom., cov: 29)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.960

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.1267+12292A>G		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.1267+12292A>G		intron_variant		2	NM_032785.4	P1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 93937 AN: 151478 Hom.: 29250 Cov.: 29

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.620 AC: 94041 AN: 151596 Hom.: 29297 Cov.: 29 AF XY: 0.618 AC XY: 45796 AN XY: 74060

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.628

Alfa AF: 0.646 Hom.: 63410

Bravo AF: 0.616

Asia WGS AF: 0.601 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.78

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: rs2798125; hg19: chr1-49040384;