rs6683832

Positions:

• chr1-62811233-G-A
• chr1-62811233-G-T

Variant summary

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

The NM_032852.4(ATG4C):​c.161-5342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,080 control chromosomes in the GnomAD database, including 31,088 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 0.64 (31088 hom., cov: 34)
• Consequence: ATG4C NM_032852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG4C	NM_032852.4	c.161-5342G>A		intron_variant		ENST00000317868.9	NP_116241.2
ATG4C	NM_178221.3	c.161-5342G>A		intron_variant			NP_835739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG4C	ENST00000317868.9	c.161-5342G>A		intron_variant		1	NM_032852.4	ENSP00000322159.4
ATG4C	ENST00000371120.7	c.161-5342G>A		intron_variant		1		ENSP00000360161.3
ATG4C	ENST00000371118.1	c.161-5342G>A		intron_variant		5		ENSP00000360159.1
ATG4C	ENST00000443289.5	c.161-5342G>A		intron_variant		2		ENSP00000396614.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96695 AN: 151962 Hom.: 31051 Cov.: 34

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.636 AC: 96784 AN: 152080 Hom.: 31088 Cov.: 34 AF XY: 0.639 AC XY: 47512 AN XY: 74340

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.639

Alfa AF: 0.608 Hom.: 3515

Bravo AF: 0.654

Asia WGS AF: 0.637 AC: 2213 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.64

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: rs6683832; hg19: chr1-63276904;