rs959145

Variant names:

• chr1-48935442-G-A
• rs959145
• NM_032785.4:c.595-68212C>T

Variant summary

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

The NM_032785.4(AGBL4):​c.595-68212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,048 control chromosomes in the GnomAD database, including 922 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 0.10 (922 hom., cov: 31)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 1 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]

ENSG00000286597 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 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.595-68212C>T		intron	N/A	NP_116174.3	Q5VU57-1
	AGBL4	NM_001323574.2		c.631-68212C>T		intron	N/A	NP_001310503.1
	AGBL4	NM_001323573.2		c.631-68212C>T		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.595-68212C>T		intron	N/A	ENSP00000360905.1	Q5VU57-1
	AGBL4	ENST00000416121.5	TSL:1	c.130-68212C>T		intron	N/A	ENSP00000401622.1	H0Y5X4
	AGBL4	ENST00000371836.1	TSL:1	c.595-68212C>T		intron	N/A	ENSP00000360902.1	B1ANV5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15872 AN: 151930 Hom.: 916 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0735

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0980

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

GnomAD4 genome AF: 0.105 AC: 15900 AN: 152048 Hom.: 922 Cov.: 31 AF XY: 0.103 AC XY: 7692 AN XY: 74332

African (AFR) AF: 0.119 AC: 4937 AN: 41476

American (AMR) AF: 0.0618 AC: 945 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3466

East Asian (EAS) AF: 0.0733 AC: 377 AN: 5142

South Asian (SAS) AF: 0.0624 AC: 300 AN: 4808

European-Finnish (FIN) AF: 0.118 AC: 1245 AN: 10574

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7351 AN: 67976

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.113 Hom.: 143

Bravo AF: 0.102

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.79
PhyloP100		-1.5
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: rs959145; hg19: chr1-49401114;