chr1-62837115-A-G

Variant names:

• chr1-62837115-A-G
• rs2886770
• NM_032852.4:c.1089+2263A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032852.4(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 NM_032852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 3 publications found

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]

ENSG00000306496 (HGNC:58931):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032852.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4C	NM_032852.4	MANE Select	c.1089+2263A>G		intron	N/A	NP_116241.2
	ATG4C	NM_178221.3		c.1089+2263A>G		intron	N/A	NP_835739.1	A0A384MTY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4C	ENST00000317868.9	TSL:1 MANE Select	c.1089+2263A>G		intron	N/A	ENSP00000322159.4	Q96DT6
	ATG4C	ENST00000371120.7	TSL:1	c.1089+2263A>G		intron	N/A	ENSP00000360161.3	Q96DT6
	ATG4C	ENST00000852843.1		c.1191+2263A>G		intron	N/A	ENSP00000522902.1

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

African (AFR) AF: 0.705 AC: 29135 AN: 41354

American (AMR) AF: 0.703 AC: 10707 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1920 AN: 3464

East Asian (EAS) AF: 0.688 AC: 3547 AN: 5154

South Asian (SAS) AF: 0.627 AC: 3012 AN: 4802

European-Finnish (FIN) AF: 0.532 AC: 5581 AN: 10482

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39289 AN: 67834

Other (OTH) AF: 0.633 AC: 1333 AN: 2106

Alfa AF: 0.600 Hom.: 3381

Bravo AF: 0.645

Asia WGS AF: 0.637 AC: 2209 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2886770; hg19: chr1-63302786;