rs742109

chr6-106146349-T-C

Variant summary

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

The ENST00000636437.1(ATG5):c.457+55623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,930 control chromosomes in the GnomAD database, including 28,145 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 0.60 (28145 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATG5	ENST00000636437.1	c.457+55623A>G		intron_variant		5
ATG5	ENST00000636335.1	c.457+55623A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91784 AN: 151812 Hom.: 28117 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.605 AC: 91849 AN: 151930 Hom.: 28145 Cov.: 31 AF XY: 0.610 AC XY: 45312 AN XY: 74272

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.602

Alfa AF: 0.609 Hom.: 38076

Bravo AF: 0.599

Asia WGS AF: 0.783 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.95
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs742109; hg19: chr6-106594224; COSMIC: COSV60263628;