1-48608973-C-T

Position:

• chr1-48608973-C-T

Variant summary

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

The NM_032785.4(AGBL4):​c.952-17988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,000 control chromosomes in the GnomAD database, including 22,309 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 0.53 (22309 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.952-17988G>A		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.952-17988G>A		intron_variant		2	NM_032785.4	ENSP00000360905	P1
AGBL4	ENST00000416121.5	c.489-17988G>A		intron_variant		1		ENSP00000401622

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80746 AN: 151882 Hom.: 22298 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.532 AC: 80805 AN: 152000 Hom.: 22309 Cov.: 32 AF XY: 0.532 AC XY: 39530 AN XY: 74280

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.540

Alfa AF: 0.557 Hom.: 6892

Bravo AF: 0.514

Asia WGS AF: 0.476 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.75

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: rs191190; hg19: chr1-49074645;