1-48608973-C-T

Variant names:

• chr1-48608973-C-T
• rs191190
• NM_032785.4:c.952-17988G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032785.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	NM_032785.4	MANE Select	c.952-17988G>A		intron	N/A	NP_116174.3	Q5VU57-1
	AGBL4	NM_001323574.2		c.988-17988G>A		intron	N/A	NP_001310503.1
	AGBL4	NM_001323573.2		c.988-17988G>A		intron	N/A	NP_001310502.1	Q5VU57-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.952-17988G>A		intron	N/A	ENSP00000360905.1	Q5VU57-1
	AGBL4	ENST00000416121.5	TSL:1	c.487-17988G>A		intron	N/A	ENSP00000401622.1	H0Y5X4

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

African (AFR) AF: 0.391 AC: 16211 AN: 41452

American (AMR) AF: 0.510 AC: 7776 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2749 AN: 5170

South Asian (SAS) AF: 0.469 AC: 2256 AN: 4812

European-Finnish (FIN) AF: 0.659 AC: 6963 AN: 10558

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41051 AN: 67968

Other (OTH) AF: 0.540 AC: 1141 AN: 2112

Alfa AF: 0.564 Hom.: 19313

Bravo AF: 0.514

Asia WGS AF: 0.476 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs191190; hg19: chr1-49074645;