dbSNP rs10489427: AGBL4:c.283-120993T>C (chr1-49366857-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032785.4(AGBL4):c.283-120993T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 152,260 control chromosomes in the GnomAD database, including 566 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 0.049 ( 566 hom., cov: 32)

Consequence

AGBL4
NM_032785.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555

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:

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new If you want to explore the variant's impact on the transcript NM_032785.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 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.283-120993T>C	intron	N/A	NP_116174.3	Q5VU57-1
AGBL4	NM_001323574.2		c.319-120993T>C	intron	N/A	NP_001310503.1
AGBL4	NM_001323573.2		c.319-120993T>C	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.283-120993T>C	intron	N/A	ENSP00000360905.1	Q5VU57-1
AGBL4	ENST00000371836.1	TSL:1	c.283-120993T>C	intron	N/A	ENSP00000360902.1	B1ANV5
AGBL4	ENST00000371838.5	TSL:5	c.283-120993T>C	intron	N/A	ENSP00000360904.1	B1AMW3

Frequencies

GnomAD3 genomes

AF:

0.0485

AC:

7376

AN:

152142

Hom.:

565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.0441

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

GnomAD4 genome

AF:

0.0486

AC:

7399

AN:

152260

Hom.:

566

Cov.:

AF XY:

0.0470

AC XY:

3496

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.160

AC:

6653

AN:

41522

American (AMR)

AF:

0.0288

AC:

440

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00262

AC:

178

AN:

68038

Other (OTH)

AF:

0.0436

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

316

631

947

1262

1578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0173

Hom.:

229

Bravo

AF:

0.0552

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

(source)

DANN

Benign

0.77

PhyloP100

0.56

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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