rs10493329

chr1-62792323-A-G

Variant summary

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

The NM_032852.4(ATG4C):c.-69+8050A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,072 control chromosomes in the GnomAD database, including 2,240 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 0.17 (2240 hom., cov: 32)
• Consequence: ATG4C NM_032852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

ATG4C (HGNC:16040): (autophagy related 4C 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 the same protein, 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG4C	NM_032852.4	c.-69+8050A>G		intron_variant		ENST00000317868.9
ATG4C	NM_178221.3	c.-69+8098A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG4C	ENST00000317868.9	c.-69+8050A>G		intron_variant		1	NM_032852.4	P1
ATG4C	ENST00000371120.7	c.-69+8098A>G		intron_variant		1		P1
ATG4C	ENST00000371118.1	c.-69+7063A>G		intron_variant		5
ATG4C	ENST00000443289.5	c.-10+8050A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25184 AN: 151954 Hom.: 2230 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.166 AC: 25218 AN: 152072 Hom.: 2240 Cov.: 32 AF XY: 0.166 AC XY: 12373 AN XY: 74318

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.0205

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.152

Alfa AF: 0.172 Hom.: 719

Bravo AF: 0.171

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.63
Dann	Benign	0.66

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: rs10493329; hg19: chr1-63257994; COSMIC: COSV58604567;