rs2886770

Positions:

• chr1-62837115-A-G
• chr1-62837115-A-T

Variant summary

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

The ENST00000317868.9(ATG4C):​c.1089+2263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,638 control chromosomes in the GnomAD database, including 30,107 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 0.63 (30107 hom., cov: 30)
• Consequence: ATG4C ENST00000317868.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG4C	NM_032852.4	c.1089+2263A>G		intron_variant		ENST00000317868.9	NP_116241.2
ATG4C	NM_178221.3	c.1089+2263A>G		intron_variant			NP_835739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG4C	ENST00000317868.9	c.1089+2263A>G		intron_variant		1	NM_032852.4	ENSP00000322159	P1
ATG4C	ENST00000371120.7	c.1089+2263A>G		intron_variant		1		ENSP00000360161	P1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95131 AN: 151520 Hom.: 30065 Cov.: 30

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.628 AC: 95224 AN: 151638 Hom.: 30107 Cov.: 30 AF XY: 0.631 AC XY: 46756 AN XY: 74088

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.633

Alfa AF: 0.595 Hom.: 3196

Bravo AF: 0.645

Asia WGS AF: 0.637 AC: 2209 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.55

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: rs2886770; hg19: chr1-63302786;