rs10888617

Positions:

• chr1-48719316-A-C
• chr1-48719316-A-G
• chr1-48719316-A-T

Variant summary

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

The NM_032785.4(AGBL4):​c.635-56075T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,006 control chromosomes in the GnomAD database, including 14,712 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 0.42 (14712 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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 = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4	c.635-56075T>G		intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6	c.635-56075T>G		intron_variant		2	NM_032785.4	P1
AGBL4	ENST00000416121.5	c.172-56075T>G		intron_variant		1
AGBL4	ENST00000371838.5	c.635-56075T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63838 AN: 151888 Hom.: 14707 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.0761

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.420 AC: 63857 AN: 152006 Hom.: 14712 Cov.: 32 AF XY: 0.407 AC XY: 30278 AN XY: 74314

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.0764

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.451

Alfa AF: 0.470 Hom.: 5508

Bravo AF: 0.411

Asia WGS AF: 0.183 AC: 643 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	0.14
DANN	Benign	0.69

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: rs10888617; hg19: chr1-49184988;