rs2103266

chr1-49556701-G-Achr1-49556701-G-C

Variant summary

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

The NM_032785.4(AGBL4):c.282+140612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,746 control chromosomes in the GnomAD database, including 22,213 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 0.52 (22213 hom., cov: 30)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.282+140612C>T		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.282+140612C>T		intron_variant		2	NM_032785.4	P1
AGBL4	ENST00000371836.1	c.282+140612C>T		intron_variant		1
AGBL4	ENST00000371838.5	c.282+140612C>T		intron_variant		5
AGBL4	ENST00000497451.1	n.249-29097C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79461 AN: 151630 Hom.: 22210 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.524 AC: 79487 AN: 151746 Hom.: 22213 Cov.: 30 AF XY: 0.521 AC XY: 38610 AN XY: 74166

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.558

Alfa AF: 0.565 Hom.: 3124

Bravo AF: 0.518

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	5.3
Dann	Benign	0.61

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: rs2103266; hg19: chr1-50022373;