Variant 1-48653455-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_032785.4(AGBL4):c.725-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 1,558,102 control chromosomes in the GnomAD database, including 575 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.027 ( 64 hom., cov: 32)

Exomes 𝑓: 0.025 ( 511 hom. )

Consequence

AGBL4
NM_032785.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.03904

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.37

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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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 1-48653455-G-A is Benign according to our data. Variant chr1-48653455-G-A is described in ClinVar as [Benign]. Clinvar id is 3055503.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0272 (4144/152260) while in subpopulation SAS AF= 0.0506 (244/4824). AF 95% confidence interval is 0.0454. There are 64 homozygotes in gnomad4. There are 2007 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4 linkuse as main transcript	c.725-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6 linkuse as main transcript	c.725-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2	NM_032785.4	P1	Q5VU57-1
AGBL4	ENST00000416121.5 linkuse as main transcript	c.262-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1
AGBL4	ENST00000371838.5 linkuse as main transcript	c.725-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4137

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0501

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0291

GnomAD3 exomes

AF:

0.0250

AC:

4358

AN:

173974

Hom.:

AF XY:

0.0269

AC XY:

2470

AN XY:

91986

show subpopulations

Gnomad AFR exome

AF:

0.0396

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.000399

Gnomad SAS exome

AF:

0.0517

Gnomad FIN exome

AF:

0.0270

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0254

AC:

35720

AN:

1405842

Hom.:

511

Cov.:

AF XY:

0.0259

AC XY:

18025

AN XY:

695332

show subpopulations

Gnomad4 AFR exome

AF:

0.0369

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.0169

Gnomad4 EAS exome

AF:

0.000161

Gnomad4 SAS exome

AF:

0.0471

Gnomad4 FIN exome

AF:

0.0241

Gnomad4 NFE exome

AF:

0.0251

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0272

AC:

4144

AN:

152260

Hom.:

Cov.:

AF XY:

0.0270

AC XY:

2007

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.0140

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.0264

Gnomad4 NFE

AF:

0.0258

Gnomad4 OTH

AF:

0.0288

Alfa

AF:

0.0206

Hom.:

Bravo

AF:

0.0253

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AGBL4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.039

dbscSNV1_RF

Benign

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over