rs3851210

chr6-106270647-C-T

Variant summary

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

The NM_004849.4(ATG5):c.478+9014G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,272 control chromosomes in the GnomAD database, including 336 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 0.056 (336 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

Genes affected

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATG5	NM_004849.4	c.478+9014G>A		intron_variant		ENST00000369076.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG5	ENST00000369076.8	c.478+9014G>A		intron_variant		1	NM_004849.4	P1

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8579 AN: 152154 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0588

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

GnomAD4 genome AF: 0.0563 AC: 8575 AN: 152272 Hom.: 336 Cov.: 32 AF XY: 0.0584 AC XY: 4346 AN XY: 74456

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0796

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.0689

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0704 Hom.: 292

Bravo AF: 0.0501

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	8.3
Dann	Benign	0.81

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: rs3851210; hg19: chr6-106718522;