1-62857072-C-T

Variant names:

• chr1-62857072-C-T
• rs1981067
• NM_032852.4:c.1210-6920C>T

Variant summary

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

The NM_032852.4(ATG4C):​c.1210-6920C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,782 control chromosomes in the GnomAD database, including 15,576 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 0.45 (15576 hom., cov: 30)
• Consequence: ATG4C NM_032852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 5 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4C	NM_032852.4	c.1210-6920C>T		intron_variant	Intron 10 of 10	ENST00000317868.9	NP_116241.2
ATG4C	NM_178221.3	c.1210-6920C>T		intron_variant	Intron 10 of 10		NP_835739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4C	ENST00000317868.9	c.1210-6920C>T		intron_variant	Intron 10 of 10	1	NM_032852.4	ENSP00000322159.4
ATG4C	ENST00000371120.7	c.1210-6920C>T		intron_variant	Intron 10 of 10	1		ENSP00000360161.3
ENSG00000306496	ENST00000819120.1	n.414+4348G>A		intron_variant	Intron 3 of 3
ENSG00000306496	ENST00000819121.1	n.324+4348G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68452 AN: 151664 Hom.: 15559 Cov.: 30

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.451 AC: 68503 AN: 151782 Hom.: 15576 Cov.: 30 AF XY: 0.453 AC XY: 33606 AN XY: 74174

African (AFR) AF: 0.467 AC: 19304 AN: 41360

American (AMR) AF: 0.506 AC: 7723 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3468

East Asian (EAS) AF: 0.658 AC: 3370 AN: 5122

South Asian (SAS) AF: 0.430 AC: 2065 AN: 4798

European-Finnish (FIN) AF: 0.393 AC: 4149 AN: 10544

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28687 AN: 67926

Other (OTH) AF: 0.481 AC: 1012 AN: 2106

Alfa AF: 0.436 Hom.: 2501

Bravo AF: 0.461

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.87
PhyloP100		-0.59
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: rs1981067; hg19: chr1-63322743;