rs4946728

Positions:

• chr6-106142488-A-C
• chr6-106142488-A-G
• chr6-106142488-A-T

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+59484T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,158 control chromosomes in the GnomAD database, including 40,627 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 0.72 (40627 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000636437.1	c.457+59484T>G		intron_variant		5		ENSP00000490376
ATG5	ENST00000636335.1	c.457+59484T>G		intron_variant, NMD_transcript_variant		5		ENSP00000490221

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110097 AN: 152040 Hom.: 40591 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.724 AC: 110187 AN: 152158 Hom.: 40627 Cov.: 32 AF XY: 0.730 AC XY: 54316 AN XY: 74376

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.744

Alfa AF: 0.753 Hom.: 73126

Bravo AF: 0.722

Asia WGS AF: 0.907 AC: 3153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4946728; hg19: chr6-106590363; COSMIC: COSV60263611;