rs4247179

chr2-241646201-G-Achr2-241646201-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013325.5(ATG4B):c.11-4809G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,052 control chromosomes in the GnomAD database, including 19,303 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 0.50 (19303 hom., cov: 32)
• Consequence: ATG4B NM_013325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

Genes affected

ATG4B (HGNC:20790): (autophagy related 4B 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. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG4B	NM_013325.5	c.11-4809G>A		intron_variant		ENST00000404914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG4B	ENST00000404914.8	c.11-4809G>A		intron_variant		1	NM_013325.5	P1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75666 AN: 151934 Hom.: 19275 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.498 AC: 75729 AN: 152052 Hom.: 19303 Cov.: 32 AF XY: 0.509 AC XY: 37814 AN XY: 74330

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.496

Alfa AF: 0.472 Hom.: 2299

Bravo AF: 0.492

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.31
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs4247179; hg19: chr2-242585616;