rs355206

Positions:

• chr1-49206502-C-A
• chr1-49206502-C-G

Variant summary

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

The NM_032785.4(AGBL4):​c.377+39268G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,816 control chromosomes in the GnomAD database, including 8,206 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 0.31 (8206 hom., cov: 31)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.377+39268G>T		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.377+39268G>T		intron_variant		2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000371836.1	c.377+39268G>T		intron_variant		1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.377+39268G>T		intron_variant		5		ENSP00000360904.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47604 AN: 151698 Hom.: 8202 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.314 AC: 47630 AN: 151816 Hom.: 8206 Cov.: 31 AF XY: 0.320 AC XY: 23761 AN XY: 74190

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.304

Alfa AF: 0.314 Hom.: 953

Bravo AF: 0.304

Asia WGS AF: 0.551 AC: 1913 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.54

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: rs355206; hg19: chr1-49672174;