chr1-62787051-A-G

Variant names:

• chr1-62787051-A-G
• rs11208029
• NM_032852.4:c.-69+2778A>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.-69+2778A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,158 control chromosomes in the GnomAD database, including 1,693 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 0.14 (1693 hom., cov: 32)
• Consequence: ATG4C NM_032852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4C	NM_032852.4	MANE Select	c.-69+2778A>G		intron	N/A	NP_116241.2
	ATG4C	NM_178221.3		c.-69+2826A>G		intron	N/A	NP_835739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4C	ENST00000317868.9	TSL:1 MANE Select	c.-69+2778A>G		intron	N/A	ENSP00000322159.4
	ATG4C	ENST00000371120.7	TSL:1	c.-69+2826A>G		intron	N/A	ENSP00000360161.3
	ATG4C	ENST00000371118.1	TSL:5	c.-69+1791A>G		intron	N/A	ENSP00000360159.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21995 AN: 152040 Hom.: 1688 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0980

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: 0.131

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

GnomAD4 genome AF: 0.145 AC: 22011 AN: 152158 Hom.: 1693 Cov.: 32 AF XY: 0.147 AC XY: 10907 AN XY: 74390

African (AFR) AF: 0.129 AC: 5342 AN: 41512

American (AMR) AF: 0.184 AC: 2814 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.0204 AC: 106 AN: 5190

South Asian (SAS) AF: 0.196 AC: 945 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10641 AN: 67980

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.133 Hom.: 631

Bravo AF: 0.148

Asia WGS AF: 0.126 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.51
PhyloP100		-1.7
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: rs11208029; hg19: chr1-63252722; COSMIC: COSV58604522;