rs6937876

chr6-106132754-G-A

Variant summary

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

The ENST00000636437.1(ATG5):c.457+69218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,152 control chromosomes in the GnomAD database, including 38,482 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 0.70 (38482 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 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+69218C>T		intron_variant		5
ATG5	ENST00000636335.1	c.458-54439C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106116 AN: 152034 Hom.: 38410 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.698 AC: 106261 AN: 152152 Hom.: 38482 Cov.: 32 AF XY: 0.694 AC XY: 51587 AN XY: 74374

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.675

Alfa AF: 0.672 Hom.: 5539

Bravo AF: 0.721

Asia WGS AF: 0.662 AC: 2304 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	0.35
Dann	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6937876; hg19: chr6-106580629; COSMIC: COSV60263571;