6-106120159-C-T

Position:

• chr6-106120159-C-T

Variant summary

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

The ENST00000636437.1(ATG5):​c.458-73334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,168 control chromosomes in the GnomAD database, including 44,979 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 0.76 (44979 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.106120159C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000636437.1	c.458-73334G>A		intron_variant		5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.458-41844G>A		intron_variant		5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115672 AN: 152050 Hom.: 44895 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.761 AC: 115823 AN: 152168 Hom.: 44979 Cov.: 32 AF XY: 0.763 AC XY: 56752 AN XY: 74396

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.746

Alfa AF: 0.696 Hom.: 57471

Bravo AF: 0.775

Asia WGS AF: 0.779 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs548234; hg19: chr6-106568034;