rs561383

Positions:

• chr1-48672507-T-G

Variant summary

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

The NM_032785.4(AGBL4):​c.635-9266A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,018 control chromosomes in the GnomAD database, including 24,183 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 0.56 (24183 hom., cov: 33)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.635-9266A>C		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.635-9266A>C		intron_variant		2	NM_032785.4	P1
AGBL4	ENST00000416121.5	c.172-9266A>C		intron_variant		1
AGBL4	ENST00000371838.5	c.635-9266A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85149 AN: 151900 Hom.: 24179 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.560 AC: 85197 AN: 152018 Hom.: 24183 Cov.: 33 AF XY: 0.558 AC XY: 41440 AN XY: 74288

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.552

Alfa AF: 0.567 Hom.: 3071

Bravo AF: 0.556

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.71

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: rs561383; hg19: chr1-49138179; COSMIC: COSV61891772;