rs4946730

Positions:

• chr6-106165216-G-A
• chr6-106165216-G-C

Variant summary

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

The ENST00000636437.1(ATG5):​c.457+36756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,938 control chromosomes in the GnomAD database, including 7,906 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 0.31 (7906 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 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+36756C>T		intron_variant		5		ENSP00000490376
ATG5	ENST00000636335.1	c.457+36756C>T		intron_variant, NMD_transcript_variant		5		ENSP00000490221

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46524 AN: 151820 Hom.: 7872 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.307 AC: 46626 AN: 151938 Hom.: 7906 Cov.: 31 AF XY: 0.303 AC XY: 22463 AN XY: 74242

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.306

Alfa AF: 0.260 Hom.: 10795

Bravo AF: 0.319

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4946730; hg19: chr6-106613091; COSMIC: COSV60263713;