rs320035

Positions:

• chr1-48623525-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032785.4(AGBL4):​c.951+10968T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,220 control chromosomes in the GnomAD database, including 20,967 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 0.50 (20967 hom., cov: 34)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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]

AGBL4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.951+10968T>C		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.951+10968T>C		intron_variant		2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000416121.5	c.486+10968T>C		intron_variant		1		ENSP00000401622.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75802 AN: 152102 Hom.: 20961 Cov.: 34

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.498 AC: 75836 AN: 152220 Hom.: 20967 Cov.: 34 AF XY: 0.499 AC XY: 37123 AN XY: 74420

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.518

Alfa AF: 0.588 Hom.: 41205

Bravo AF: 0.478

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.86

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: rs320035; hg19: chr1-49089197; COSMIC: COSV61891516;