rs9659092

Variant names:

• chr1-49977917-A-G
• rs9659092
• NM_032785.4:c.34+45846T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032785.4(AGBL4):​c.34+45846T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,046 control chromosomes in the GnomAD database, including 15,314 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 0.40 (15314 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.34+45846T>C		intron_variant	Intron 1 of 13	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.34+45846T>C		intron_variant	Intron 1 of 13	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000371836.1	c.34+45846T>C		intron_variant	Intron 1 of 6	1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.34+45846T>C		intron_variant	Intron 1 of 8	5		ENSP00000360904.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60472 AN: 151928 Hom.: 15315 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.398 AC: 60468 AN: 152046 Hom.: 15314 Cov.: 32 AF XY: 0.392 AC XY: 29164 AN XY: 74324

African (AFR) AF: 0.105 AC: 4377 AN: 41498

American (AMR) AF: 0.464 AC: 7085 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2039 AN: 3470

East Asian (EAS) AF: 0.0399 AC: 207 AN: 5184

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4822

European-Finnish (FIN) AF: 0.482 AC: 5085 AN: 10552

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38113 AN: 67930

Other (OTH) AF: 0.445 AC: 940 AN: 2110

Alfa AF: 0.519 Hom.: 10971

Bravo AF: 0.382

Asia WGS AF: 0.200 AC: 699 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	3.6
DANN	Benign	0.70
PhyloP100		0.54
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: rs9659092; hg19: chr1-50443589;