rs320035

Variant names:

• chr1-48623525-A-G
• rs320035
• NM_032785.4:c.951+10968T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032785.4(AGBL4):​c.951+10968T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,220 control chromosomes in the GnomAD database, including 20,967 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 0.50 (20967 hom., cov: 34)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 7 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=-0.2).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	NM_032785.4	MANE Select	c.951+10968T>C		intron	N/A	NP_116174.3
	AGBL4	NM_001323574.2		c.987+10968T>C		intron	N/A	NP_001310503.1
	AGBL4	NM_001323573.2		c.987+10968T>C		intron	N/A	NP_001310502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.951+10968T>C		intron	N/A	ENSP00000360905.1
	AGBL4	ENST00000416121.5	TSL:1	c.486+10968T>C		intron	N/A	ENSP00000401622.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75802 AN: 152102 Hom.: 20961 Cov.: 34

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.498 AC: 75836 AN: 152220 Hom.: 20967 Cov.: 34 AF XY: 0.499 AC XY: 37123 AN XY: 74420

African (AFR) AF: 0.258 AC: 10701 AN: 41554

American (AMR) AF: 0.528 AC: 8071 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2074 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1573 AN: 5164

South Asian (SAS) AF: 0.580 AC: 2803 AN: 4832

European-Finnish (FIN) AF: 0.664 AC: 7028 AN: 10590

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41605 AN: 67996

Other (OTH) AF: 0.518 AC: 1095 AN: 2112

Alfa AF: 0.559 Hom.: 65100

Bravo AF: 0.478

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.86
PhyloP100		3.3
Mutation Taster		=98/2	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: rs320035; hg19: chr1-49089197; COSMIC: COSV61891516;