1-49639529-T-C

Variant names:

• chr1-49639529-T-C
• rs2051086
• NM_032785.4:c.282+57784A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032785.4(AGBL4):​c.282+57784A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,062 control chromosomes in the GnomAD database, including 35,743 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 0.68 (35743 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.282+57784A>G		intron_variant	Intron 3 of 13	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.282+57784A>G		intron_variant	Intron 3 of 13	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000371836.1	c.282+57784A>G		intron_variant	Intron 3 of 6	1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.282+57784A>G		intron_variant	Intron 3 of 8	5		ENSP00000360904.1
AGBL4	ENST00000497451.1	n.248+57784A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103082 AN: 151944 Hom.: 35707 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.678 AC: 103171 AN: 152062 Hom.: 35743 Cov.: 32 AF XY: 0.671 AC XY: 49902 AN XY: 74316

African (AFR) AF: 0.773 AC: 32053 AN: 41486

American (AMR) AF: 0.677 AC: 10332 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3470

East Asian (EAS) AF: 0.271 AC: 1395 AN: 5150

South Asian (SAS) AF: 0.539 AC: 2603 AN: 4830

European-Finnish (FIN) AF: 0.613 AC: 6480 AN: 10574

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45447 AN: 67972

Other (OTH) AF: 0.691 AC: 1459 AN: 2112

Alfa AF: 0.654 Hom.: 14508

Bravo AF: 0.689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.51
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2051086; hg19: chr1-50105201;