1-62838174-C-T

Variant names:

• chr1-62838174-C-T
• rs10493327
• NM_032852.4:c.1090-3254C>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.1090-3254C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,784 control chromosomes in the GnomAD database, including 15,896 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 0.46 (15896 hom., cov: 31)
• Consequence: ATG4C NM_032852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4C	NM_032852.4	c.1090-3254C>T		intron_variant	Intron 9 of 10	ENST00000317868.9	NP_116241.2
ATG4C	NM_178221.3	c.1090-3254C>T		intron_variant	Intron 9 of 10		NP_835739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4C	ENST00000317868.9	c.1090-3254C>T		intron_variant	Intron 9 of 10	1	NM_032852.4	ENSP00000322159.4
ATG4C	ENST00000371120.7	c.1090-3254C>T		intron_variant	Intron 9 of 10	1		ENSP00000360161.3
ENSG00000306496	ENST00000819120.1	n.414+23246G>A		intron_variant	Intron 3 of 3
ENSG00000306496	ENST00000819121.1	n.324+23246G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69156 AN: 151666 Hom.: 15876 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.456 AC: 69209 AN: 151784 Hom.: 15896 Cov.: 31 AF XY: 0.458 AC XY: 33962 AN XY: 74190

African (AFR) AF: 0.481 AC: 19883 AN: 41376

American (AMR) AF: 0.508 AC: 7747 AN: 15256

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

East Asian (EAS) AF: 0.668 AC: 3442 AN: 5156

South Asian (SAS) AF: 0.432 AC: 2082 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4151 AN: 10508

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

European-Non Finnish (NFE) AF: 0.423 AC: 28692 AN: 67888

Other (OTH) AF: 0.482 AC: 1017 AN: 2108

Alfa AF: 0.436 Hom.: 43905

Bravo AF: 0.466

Asia WGS AF: 0.505 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.55
DANN	Benign	0.23
PhyloP100		-0.44
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: rs10493327; hg19: chr1-63303845;