1-49719403-A-G

Position:

• chr1-49719403-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.158-21966T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,986 control chromosomes in the GnomAD database, including 16,186 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 0.42 (16186 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.158-21966T>C		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.158-21966T>C		intron_variant		2	NM_032785.4	P1
AGBL4	ENST00000371836.1	c.158-21966T>C		intron_variant		1
AGBL4	ENST00000371838.5	c.158-21966T>C		intron_variant		5
AGBL4	ENST00000497451.1	n.124-21966T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64427 AN: 151866 Hom.: 16186 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.424 AC: 64427 AN: 151986 Hom.: 16186 Cov.: 32 AF XY: 0.418 AC XY: 31075 AN XY: 74292

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.467

Alfa AF: 0.538 Hom.: 30805

Bravo AF: 0.413

Asia WGS AF: 0.204 AC: 713 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
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: rs11205641; hg19: chr1-50185075;