Genetic Variant AGBL4:c.594+19879C>G (chr1-49025705-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032785.4(AGBL4):c.594+19879C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,100 control chromosomes in the GnomAD database, including 55,106 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 0.85 ( 55106 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

AGBL4
NM_032785.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.188

Publications

1 publications found

Variant links:

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]

AGBL4 links:

ENSG00000229846 (HGNC:):

ENSG00000229846 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.888 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGBL4	NM_032785.4	MANE Select	c.594+19879C>G	intron	N/A	NP_116174.3	Q5VU57-1
AGBL4	NM_001323574.2		c.630+19879C>G	intron	N/A	NP_001310503.1
AGBL4	NM_001323573.2		c.630+19879C>G	intron	N/A	NP_001310502.1	Q5VU57-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.594+19879C>G	intron	N/A	ENSP00000360905.1	Q5VU57-1
AGBL4	ENST00000416121.5	TSL:1	c.129+19879C>G	intron	N/A	ENSP00000401622.1	H0Y5X4
AGBL4	ENST00000371836.1	TSL:1	c.594+19879C>G	intron	N/A	ENSP00000360902.1	B1ANV5

Frequencies

GnomAD3 genomes

AF:

0.849

AC:

129074

AN:

151982

Hom.:

55076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.940

Gnomad AMR

AF:

0.875

Gnomad ASJ

AF:

0.897

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.824

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.879

Gnomad NFE

AF:

0.894

Gnomad OTH

AF:

0.870

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.849

AC:

129156

AN:

152100

Hom.:

55106

Cov.:

AF XY:

0.844

AC XY:

62782

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.790

AC:

32744

AN:

41474

American (AMR)

AF:

0.875

AC:

13369

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.897

AC:

3114

AN:

3472

East Asian (EAS)

AF:

0.680

AC:

3512

AN:

5162

South Asian (SAS)

AF:

0.823

AC:

3968

AN:

4820

European-Finnish (FIN)

AF:

0.825

AC:

8733

AN:

10582

Middle Eastern (MID)

AF:

0.877

AC:

256

AN:

292

European-Non Finnish (NFE)

AF:

0.894

AC:

60765

AN:

67994

Other (OTH)

AF:

0.869

AC:

1838

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

973

1947

2920

3894

4867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.871

Hom.:

7180

Bravo

AF:

0.850

Asia WGS

AF:

0.738

AC:

2566

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.8

(source)

DANN

Benign

0.66

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over