Variant NM_052936.5:c.1126+48G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_052936.5(ATG4A):c.1126+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 906,757 control chromosomes in the GnomAD database, including 71,456 homozygotes. There are 115,420 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 10721 hom., 15884 hem., cov: 23)

Exomes 𝑓: 0.45 ( 60735 hom. 99536 hem. )

Consequence

ATG4A
NM_052936.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.441

Variant links:

Genes affected

ATG4A (HGNC:16489): (autophagy related 4A cysteine peptidase) Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. [provided by RefSeq, Mar 2016]

ATG4A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-108153135-G-A is Benign according to our data. Variant chrX-108153135-G-A is described in ClinVar as [Benign]. Clinvar id is 2688198.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4A	NM_052936.5 link	c.1126+48G>A		intron_variant	Intron 12 of 12	ENST00000372232.8	NP_443168.2	Q8WYN0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4A	ENST00000372232.8 link	c.1126+48G>A		intron_variant	Intron 12 of 12	1	NM_052936.5	ENSP00000361306.3		Q8WYN0-1

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

54933

AN:

110365

Hom.:

10713

Cov.:

AF XY:

0.485

AC XY:

15839

AN XY:

32639

show subpopulations

Gnomad AFR

AF:

0.680

Gnomad AMI

AF:

0.804

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.430

GnomAD3 exomes

AF:

0.414

AC:

62245

AN:

150306

Hom.:

10520

AF XY:

0.417

AC XY:

17849

AN XY:

42758

show subpopulations

Gnomad AFR exome

AF:

0.692

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.597

Gnomad NFE exome

AF:

0.478

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.449

AC:

357206

AN:

796335

Hom.:

60735

Cov.:

AF XY:

0.468

AC XY:

99536

AN XY:

212861

show subpopulations

Gnomad4 AFR exome

AF:

0.686

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.590

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.498

AC:

54983

AN:

110422

Hom.:

10721

Cov.:

AF XY:

0.486

AC XY:

15884

AN XY:

32708

show subpopulations

Gnomad4 AFR

AF:

0.680

Gnomad4 AMR

AF:

0.264

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.591

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.434

Alfa

AF:

0.456

Hom.:

30388

Bravo

AF:

0.481

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 37% of patients studied by a panel of primary immunodeficiencies. Number of patients: 35. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.045

DANN

Benign

0.51

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

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