rs1925425

Variant names:

• chr1-48979662-A-T
• rs1925425
• NM_032785.4:c.594+65922T>A

Variant summary

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

The NM_032785.4(AGBL4):​c.594+65922T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,808 control chromosomes in the GnomAD database, including 22,538 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 0.54 (22538 hom., cov: 30)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.594+65922T>A		intron_variant	Intron 5 of 13	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.594+65922T>A		intron_variant	Intron 5 of 13	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000416121.5	c.129+65922T>A		intron_variant	Intron 1 of 6	1		ENSP00000401622.1
AGBL4	ENST00000371836.1	c.594+65922T>A		intron_variant	Intron 5 of 6	1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.594+65922T>A		intron_variant	Intron 5 of 8	5		ENSP00000360904.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82167 AN: 151690 Hom.: 22519 Cov.: 30

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.542 AC: 82238 AN: 151808 Hom.: 22538 Cov.: 30 AF XY: 0.538 AC XY: 39920 AN XY: 74184

African (AFR) AF: 0.517 AC: 21412 AN: 41402

American (AMR) AF: 0.577 AC: 8798 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1786 AN: 3464

East Asian (EAS) AF: 0.209 AC: 1077 AN: 5162

South Asian (SAS) AF: 0.474 AC: 2276 AN: 4804

European-Finnish (FIN) AF: 0.560 AC: 5900 AN: 10528

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39063 AN: 67878

Other (OTH) AF: 0.553 AC: 1168 AN: 2112

Alfa AF: 0.556 Hom.: 2898

Bravo AF: 0.541

Asia WGS AF: 0.336 AC: 1168 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.3
DANN	Benign	0.69
PhyloP100		0.31
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: rs1925425; hg19: chr1-49445334;